{"@context":"https://w3id.org/ro/crate/1.1/context","@type":"Dataset","id":"467ebee6-15d2-4907-bf9c-0b97ec47f608","name":"Research Synthesis: Statin Use Effects — full paper","doi":"10.17605/OSF.IO/879A6","doi_status":"minted","osf_url":"https://osf.io/879a6/","dw_chain_url":"https://provenance.researka.org/artifacts/claim_3e8750bd30ae4a7e/chain","content_hash":"sha256:79a56f16017718c78f189593facd2a6e0876765426cea41712d10c931f5de76e","provenance_passport":{"publication_id":"467ebee6-15d2-4907-bf9c-0b97ec47f608","submission_id":"a732dfb7-4dd1-4bd7-9e67-ab69b81d1b09","artifact_type":"research_paper","decision":"accept","content_hash":"sha256:79a56f16017718c78f189593facd2a6e0876765426cea41712d10c931f5de76e","persistent_identifiers":{"doi":"10.17605/OSF.IO/879A6","osf_url":"https://osf.io/879a6/","orcid":null,"ror_id":null,"raid_id":null},"persistent_identifier_status":{"doi":"supplied","osf_url":"supplied","orcid":"not_supplied","ror_id":"not_supplied","raid_id":"not_supplied"},"institution":{"name":null,"ror_id":null,"status":"not_supplied"},"integrity":null,"provenance":{"dw_artifact_id":"claim_3e8750bd30ae4a7e","dw_chain_url":"https://provenance.researka.org/artifacts/claim_3e8750bd30ae4a7e/chain"},"timeline":["submission_intake","autonomous_review","autonomous_editorial_decision","autonomous_publish"]},"publication":{"id":"467ebee6-15d2-4907-bf9c-0b97ec47f608","object_type":"publication","parent_object_id":"a732dfb7-4dd1-4bd7-9e67-ab69b81d1b09","title":"Research Synthesis: Statin Use Effects — full paper","body_markdown":"# Research Synthesis: Statin Use Effects — full paper\n\n## Abstract\n\nEvidence-honesty note: 38/65 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.\n\nThis paper synthesizes evidence on statin use effects across 65 accepted source papers and 3513 high-confidence extracted claims.\n\nThe evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 37 adjacent clinical sources, and 2 mechanistic or model-system sources, with 592 cross-study disagreements across the evidence base.\n\nPositive study-level signals are summarized in the longevity, mortality and survival, cardiometabolic outcome classes, null signals in the contextual adjacent evidence, mortality and survival, safety and comorbidity outcome classes, and negative signals in the cardiometabolic outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.\n\nThe conclusion is that statin use effects remains a bounded geroscience case: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.\n\nThis conservative interpretation is especially important in aging research because endpoints often differ across model systems, human trials, and observational cohorts. A signal in one domain does not automatically establish the same signal in another.\n\n## Introduction\n\nThe global burden of age-related disease continues to mount as populations grow older, creating an urgent search for interventions that might compress morbidity and extend healthspan rather than merely treating individual conditions in isolation. Statins — 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors — occupy a unique position in this landscape because they are among the most widely prescribed medications worldwide, with an estimated hundreds of millions of patient-years of accumulated exposure, and their primary cardiovascular indications already encompass a large share of the older-adult population. Yet the question of whether Statin Use Effects extend beyond low-density lipoprotein lowering to influence fundamental aging biology has gained considerable momentum over the past decade, fueled by observational signals linking statin use to reduced mortality in diverse clinical contexts ranging from sepsis to cancer. Whether these associations represent genuine geroprotective activity, residual confounding by indication, or selective survivorship bias remains deeply uncertain, and the stakes are high: if even a fraction of the observed benefit reflects true anti-aging mechanisms, the public-health implications for a low-cost, globally accessible drug class would be substantial. At the same time, concerns about Statin Use Effects on muscle function, gait speed, and sarcopenia risk in older adults raise the possibility that any longevity gain could be offset by accelerated physical decline — a tradeoff that is especially consequential for frail or mobility-limited individuals. The present moment therefore demands a structured, cross-domain evidence synthesis that can weigh competing signals rather than relying on any single outcome class to define the overall risk–benefit profile of Statin Use Effects.\n\nSeveral unresolved questions complicate efforts to draw definitive conclusions about Statin Use Effects as a geroprotective strategy, and these uncertainties span mechanistic plausibility, clinical translation, and population specificity. The dose-response and duration-response relationships for both benefits and harms remain poorly characterized: some evidence suggests that higher statin doses may carry greater osteoarthritis risk (Zhang 2022), while cancer-related benefits in colorectal cancer may be duration-dependent (Sun 2023), but these findings require replication in prospective designs. Additionally, the question of whether Statin Use Effects differ meaningfully between primary and secondary prevention contexts, or between younger and older subpopulations, has been raised but not resolved, as most meta-analytic estimates pool across these strata. Concomitant medication use represents another underexplored confounder; one study found that the association between statin use and gait speed reserve was modified by the presence of other cardiovascular medications (Spiegeleer 2025). Finally, the potential for statin use to increase the risk of daptomycin-related rhabdomyolysis (Chuma 2022) or to influence the incidence of specific conditions such as microscopic colitis (Rancz 2025) underscores that the safety profile of long-term statin use in aging populations may be more complex than the cardiovascular-focused risk–benefit calculus that currently dominates clinical guidelines.\n\nThe present synthesis aims to address these cross-domain tensions by applying a structured evidence-weighting framework that explicitly separates clinical-effect estimates from mechanistic rationale, and that maps the concordance or discordance of Statin Use Effects across multiple aging-relevant outcome classes simultaneously. Rather than treating longevity, cardiometabolic health, muscle function, cancer prognosis, and safety as independent literatures, this approach examines whether signals in one domain are reinforced or contradicted by findings in another — for example, whether the positive mortality associations observed in sepsis and cancer cohorts are compatible with the negative muscle-function signals reported in community-dwelling older adults. The synthesis draws on approximately 65 curated reference papers spanning observational cohorts, systematic reviews, and meta-analyses, and identifies hundreds of cross-study disagreements across outcome classes that collectively define the current evidence boundary for Statin Use Effects as an anti-aging intervention. By foregrounding these tensions rather than averaging across them, the framework is designed to help clinicians and researchers distinguish between contexts in which statin use appears to confer broad-spectrum benefit and those in which the evidence remains ambiguous or points toward net harm. The central argument is not that statins are or are not geroprotectors, but rather that the case for geroprotection is currently incomplete: mechanistic plausibility coexists with mixed human evidence, and the boundary conditions — encompassing population, duration, dose, statin type, and competing risk — remain to be systematically established. This structured approach is intended to inform both clinical decision-making for older adults already taking statins and the design of future trials that could definitively test the geroprotective hypothesis.\n\n## Background\n\nPreclinical and disease-model evidence suggests that statins modulate pathways relevant to aging biology, though effect directions vary by context. In colorectal cancer models, statin exposure has been associated with improved prognosis, including reduced all-cause mortality (HR: 0.80; 95% CI: 0.74-0.87) and cancer-specific mortality (HR: 0.74; 95% CI: 0.67-0.82), though heterogeneity across studies was substantial (I² = 90% and I² = 88%, respectively) (Vahed 2026). Prostate cancer analyses report a similar survival signal in men receiving androgen-deprivation therapy, with a pooled 27% reduction in overall mortality risk (Jayalath 2022). Thus, Statin Use Effects appear to operate along a mechanistic duality: anti-neoplastic and anti-inflammatory pathways may be enhanced, while skeletal muscle function may be compromised.\n\nMethodological questions critically shape interpretation of the Statin Use Effects literature and illuminate the mechanism-to-clinic gap. Endpoint selection is a major source of heterogeneity: mortality-survival outcomes range from 30-day in-hospital death to long-term cancer-specific survival, each with distinct confounding structures. Muscle-function endpoints such as grip strength, gait speed, and appendicular lean mass may be sensitive to pharmacogenomic variability, though Statin Use Effects on decline persisted irrespective of pharmacogenomic score in at least one large analysis (Gentreau 2025). The overall synthesis suggests that while Statin Use Effects are biologically plausible across multiple aging-related domains, the evidence remains fragmented by heterogeneous methods, variable follow-up durations, and the absence of large-scale randomized trials testing geriatric-specific endpoints—leaving the anti-aging hypothesis as currently constituted incomplete.\n\n### Evidence Context\n\nThe evidence context combines established clinical use, adjacent human\nevidence, animal or cellular mechanisms, and open translational\nquestions. Separating those evidence types prevents later sections from\ncollapsing unlike forms of support into a single verdict. The central\nresearch problem remains whether mechanistic plausibility and\nsource-traced findings converge strongly enough to justify further\nclinical testing while keeping patient-facing claims conservative.\n\nThe biological rationale is treated as context rather than as clinical proof. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation\nseparates direct clinical findings from mechanistic and adjacent evidence,\npreserving uncertainty where endpoint, population, comparator, or follow-up\ndiffers. This conservative boundary keeps the scientific question visible\nwithout inserting unsupported numeric detail or stronger causal language than\nthe retained evidence allows. Where studies point in different directions,\nthe synthesis treats that disagreement as information about design and\napplicability rather than as noise. The key question becomes which population,\nintervention schedule, comparator, and endpoint layer would be required for the\nclaim to survive a prospective test. This preserves the practical implication\nfor readers: favorable signals can justify targeted follow-up, while unresolved\ntradeoffs still limit broad clinical or public-health recommendations.\n\n## Methods\n\n### Review type and protocol\nThis manuscript is reported as a PRISMA-ScR structured scoping synthesis. A deterministic protocol governed source retrieval, screening, extraction, and synthesis; the protocol was frozen before manuscript rendering. The full audit trail is in the supplementary `methods_pack.json` and the timestamped submission directory `synthesis-statin_use_effects-v06-DAILY-2026-06-09T04-57-10Z-R2`.\n\n### Information sources\nSources were retrieved across PubMed, Europe PMC, OpenAlex, Semantic Scholar, Crossref, DOAJ, OpenAIRE, PMC OAI, bioRxiv, medRxiv, arXiv, and ClinicalTrials.gov. Retrieval window: 2026-06-09.\n\n### Search strategy\nThe following topic-anchored queries were executed against the information sources listed above:\n\n- `statin use effects aging`\n- `statin use effects older adults`\n- `statin use effects randomized controlled trial`\n- `statin use aging`\n- `statin use older adults`\n- `statin use randomized controlled trial`\n\n### Eligibility criteria\n- Sources whose primary content addresses statin use effects.\n- Sources with extractable quantitative or qualitative findings.\n- Peer-reviewed primary research, systematic reviews, or meta-analyses; preprints accepted only when source-traceable.\n- Sources with verifiable bibliographic identifiers (DOI / PMID / canonical handle).\n\n### Selection of sources of evidence\nThe synthesis did not begin from an unfiltered database export. It began from a pre-curated receipt-candidate set generated by the retrieval and claim-binding pipeline. Of 195 records in the receipt-candidate union, 75 were classified as source candidates and 65 were admitted as traceable synthesis sources. Mixed partial-or-none and partial-only rows are separate claim-binding audit buckets, not additive exclusion totals. No additional records were excluded after final source admission.\n\n### source admission funnel\n\n| Admission bucket | n |\n|---|---:|\n| Receipt candidate union | 195 |\n| Classified source candidates | 75 |\n| No extractable claims | 5 |\n| None-only claim binding | 3 |\n| Mixed partial-or-none claim-binding candidates | 82 |\n| Partial-only claim-binding candidates | 11 |\n| Strict high-confidence sources | 19 |\n| Admitted final sources | 65 |\n\n### Exclusion reasons\n- Non-traceable findings (claim could not be linked to source text): 0 records.\n- Wrong population / off-topic sources excluded at screening.\n- Duplicate records deduplicated by DOI / PMID before screening.\n\n### Data items\nThe following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.\n\n### Risk-of-bias appraisal\nPer-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`.\n\n### Synthesis approach\nEvidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, longevity, mortality and survival, muscle function, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.\n\n### AI-use disclosure\nSource retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.\n\n### Accountability\nAccountability is established through reproducible artifacts: a deterministic protocol (`methods_pack.json`), a complete claim and citation registry, extracted numeric trace, deterministic gates (`full_paper.journal_surface.json`, `pre_submit_gate.json`, `artifact_consistency.json`), and a versioned correction path documented in the run's submission record. This run is certified under the `researka_agent_certified` accountability model — trust is machine-verifiable rather than dependent on author signoff.\n\n## Results\n| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |\n|---|---|---|---|---|\n| Contextual Adjacent Evidence | n=32; claims=1343 | no extracted directional signal in 24/32 sources | 15 indirect; 1 mechanistic; 16 review | limited corpus depth in this outcome class |\n| Longevity | n=13; claims=747 | unclear signal in 4/13 sources | 5 indirect; 8 review | limited corpus depth in this outcome class |\n| Mortality and Survival | n=6; claims=229 | no extracted directional signal in 4/6 sources | 5 indirect; 1 review | limited corpus depth in this outcome class |\n| Safety and Comorbidity | n=5; claims=238 | no extracted directional signal in 3/5 sources | 3 indirect; 2 review | limited corpus depth in this outcome class |\n| Cardiometabolic | n=4; claims=859 | unclear signal in 1/4 sources | 4 indirect | limited corpus depth in this outcome class |\n| Muscle Function | n=4; claims=88 | no extracted directional signal in 3/4 sources | 4 indirect | limited corpus depth in this outcome class |\n| Deficiency Prevalence | n=1; claims=9 | no extracted directional signal in 1/1 sources | 1 indirect | single-source slice; hypothesis-generating |\n\n**Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.\n\n### Cardiometabolic Outcomes\n\nThe reviewed observational cohorts examined statin use across diverse clinical contexts, from primary cardiovascular prevention to acute cerebrovascular and oncologic outcomes. Sarraju 2024 assessed guideline-directed statin use and LDL-c control in adults at 1 year after incident atherosclerotic cardiovascular disease (ASCVD). Spiegeleer 2025 evaluated the association between statin use and gait speed reserve (GSR) in older adults, examining effects of concomitant medication. Chen 2026 investigated statin therapy and 30-day all-cause mortality in patients with acute kidney injury after intracerebral hemorrhage (ICH). Maurer 2025 examined the association of statin use on survival outcomes in patients with early-stage HER2-positive breast cancer from the APHINITY trial.\n\nQuantitative findings across these cohorts reveal divergent effect directions.\n\nMechanistically, the functional decline observed by Spiegeleer 2025 in older adults aligns with proposed statin-associated myopathy pathways, where mitochondrial dysfunction and reduced CoQ10 bioavailability may impair muscle energetics, affecting gait performance. The protective signal in the acute ICH setting from Chen 2026 is consistent with pleiotropic effects of statins, including anti-inflammatory and endothelial stabilization properties that may mitigate secondary injury cascades in the cerebrovascular milieu. The null findings in the oncologic cohort of Maurer 2025 suggest that any potential statin effects on cancer cell proliferation via HMG-CoA reductase inhibition may not translate to clinically meaningful survival benefits in early-stage HER2-positive breast cancer.\n\nThis discordance underscores the context-dependency of statin effects, where benefits observed in acute, severe cerebrovascular injury may not extend to functional outcomes in community-dwelling older adults. The observational design of all four studies precludes causal inference, and the effect directions (positive, negative, null, unclear) highlight the heterogeneous impact of statins across different patient populations, disease stages, and clinical endpoints.\n\n### Contextual Adjacent Evidence Outcomes\n\nThe corpus comprises predominantly observational cohort studies and systematic reviews examining statin effects across diverse clinical contexts, including cancer prognosis, cardiovascular calcification, neuropsychiatric outcomes, and metabolic disease. Study designs included population-based cohort studies in dialysis patients (Lee 2023), target trial emulations in community-dwelling older adults (Debele 2026), and multicenter retrospective observational studies (Takechi 2025). The outcome class encompasses cancer-specific survival endpoints, cardiovascular imaging biomarkers, neurological disease risk, and treatment-related toxicities.\n\nMechanistically, the anti-cancer effects of statins have been attributed to inhibition of the mevalonate pathway, which suppresses Rho GTPase signaling and may reduce tumor cell proliferation and metastatic potential. Preclinical data from Yin 2022 suggest associations with reduced biochemical recurrence after curative prostate cancer treatment (P < 0.01 in certain subgroup analyses), supporting a biological plausibility for statin-mediated anti-neoplastic effects. Prior statin use was associated with lower in-hospital arrhythmia incidence in acute coronary syndrome (Wibawa 2023, P < 0.00001). Dong 2025 found that pre-stroke statin use influenced intracranial atherosclerotic plaque characteristics with P < 0.001 for plaque burden differences.\n\nWithin-corpus tensions are evident across several clinical domains. In the cardiovascular domain, Shahraki 2023 noted the paradox of statin-associated coronary calcification alongside cardioprotective arrhythmia reduction (Wibawa 2023). These discrepancies likely reflect differences in patient populations, statin types and doses, outcome definitions, and the inherent limitations of observational designs.\n\n### Deficiency Prevalence Outcomes\n\nThe observational cohort study by Ha 2024 evaluated the effects of statin use on serum creatinine phosphokinase (CPK) levels in adults with normal thyroid function. Daily administration across all intensity tiers was associated with measurable changes in CPK, a widely used biomarker for skeletal muscle injury and a key clinical indicator of statin-associated myopathy.\n\nConcomitant CPK elevations were observed, and the between-group difference at baseline reached statistical significance (P < 0.001), supporting the hypothesis that higher-intensity statin therapy may carry a greater burden of subclinical skeletal muscle stress. These findings are consistent with the known pharmacological mechanism whereby HMG-CoA reductase inhibition depletes intracellular mevalonate pathway intermediates critical for mitochondrial function in myocytes. The effect direction was classified as null for the broader deficiency prevalence outcome class, suggesting that while CPK changes are detectable, they may not cross clinical diagnostic thresholds for frank myopathy in most patients.\n\nMechanistically, statin-associated CPK elevation is hypothesized to stem from impaired CoQ10 biosynthesis and reduced mitochondrial electron transport chain efficiency, both downstream consequences of mevalonate pathway blockade. The Ha 2024 findings in adults with preserved thyroid function are particularly relevant because thyroid dysfunction independently elevates CPK, meaning this cohort isolates the statin-specific signal more cleanly than mixed-population studies. This mechanistic substrate connects the deficiency prevalence outcome class to broader concerns about statin tolerability, as even subclinical CPK elevations may predict treatment discontinuation in clinical practice. Integrating the Ha 2024 observational data with the broader corpus suggests that routine CPK monitoring in high-intensity statin users warrants prospective evaluation in dedicated clinical RCTs.\n\nBy contrast, the evidence base for statin-related muscle effects remains heterogeneous across the curated corpus, and the Ha 2024 null effect-direction classification for deficiency prevalence underscores a key tension: detectable biochemical CPK changes may not translate into clinically meaningful myopathy in population-level analyses. The Statin Use Effects anti-aging case as currently constituted is incomplete, and the CPK data from Ha 2024 illustrate this gap — mechanistic plausibility for statin-induced muscle stress coexists with observational null findings at the clinical outcome level. Future research linking serial CPK trajectories to patient-reported muscle symptoms in statin-treated cohorts would help clarify whether the observed P < 0.001 baseline differences carry downstream clinical relevance.\n\n### Longevity Outcomes\n\nThe corpus includes twelve studies that evaluated statin use and longevity or all-cause mortality across diverse populations and clinical settings.\n\nQuantitative findings across the corpus yielded predominantly favorable effect estimates, though confidence intervals frequently crossed unity. Multiple meta-analyses reported significant p-values including P < 0.01 across cardiovascular primary prevention endpoints (Huang 2022) and P < 0.0001 for prostate cancer mortality reduction (Hou 2022).\n\nMechanistically, the longevity signal is consistent with pleiotropic anti-inflammatory and endothelial-protective effects of statins that extend beyond lipid lowering. In clinical RCTs, the seepsis mortality benefit aligns with preclinical data demonstrating reduced inflammatory cytokine cascading (Philippou 2025). The cardiovascular primary prevention meta-analysis by Huang 2022 synthesized observational studies from PubMed, EMBASE, Cochrane Library, and Web of Science, showing consistent risk reduction across multiple endpoints with P < 0.01 for cardiovascular events. Yang 2022b documented that statin use reduced ischemic stroke risk in diabetic primary prevention populations (RR = 0.83) alongside all-cause mortality reduction (P < 0.0001). Braun 2023 found that statin use before lower-limb arterial angioplasty improved primary patency and reduced mortality, with effects reaching P < 0.00001 for certain endpoints. Breast cancer analyses (Jia 2023) showed associations between statin use and reduced recurrence and mortality using random-effects models calculating pooled hazard ratios, with multiple endpoints reaching P = 0.001 to P < 0.001.\n\n### Mortality and Survival Outcomes\n\nThe corpus identified six observational cohort studies examining the association between statin use and mortality or survival outcomes across diverse clinical populations (Stepien 2022; Scott 2025; Abuhelwa 2025; Jayalath 2022; Malmquist 2026; Sood 2023). These studies encompassed adults with cancer-related diagnoses including acute myocardial infarction in cancer patients (Stepien 2022), breast cancer (Scott 2025), chronic lymphocytic leukemia or small lymphocytic lymphoma treated with ibrutinib (Abuhelwa 2025), and advanced prostate cancer receiving androgen-ablative therapies (Jayalath 2022). All studies employed observational cohort designs with varying follow-up durations, and none constituted a randomized clinical trial of statin therapy specifically powered for mortality endpoints.\n\nQuantitative findings across these cohorts were heterogeneous. Per-study endpoint details and individual p-values are catalogued in the evidence synthesis.\n\nMechanistically, the observed survival associations may relate to pleiotropic effects of statins beyond lipid lowering, including anti-inflammatory and immunomodulatory properties that could influence cancer progression and cardiovascular event rates. Systematic review data from Scott 2025 supported a protective association between statin use and breast cancer-specific mortality and recurrence, though the analysis acknowledged concerns about immortal time bias. Preclinical and mechanistic human studies suggest statins may modulate tumor biology through Rho GTPase inhibition and reduced mevalonate pathway flux, yet the translation of these effects into consistent clinical mortality benefit remains uncertain.\n\nWithin the corpus, a clear tension exists between studies reporting positive mortality associations and those reporting null findings. These disagreements likely reflect differences in population characteristics, statin timing and duration, underlying disease states, and potential confounding by indication, underscoring that the mortality-survival signal is context-dependent rather than universal across clinical settings.\n\n### Muscle Function Outcomes\n\nFour observational cohorts examined the relationship between statin use and muscle-related outcomes in adult populations. Veddeng 2022 studied home-dwelling older patients receiving polypharmacy, while Bae 2024 conducted a meta-epidemiological synthesis of retrospective cohort studies on statin-associated outcomes.\n\nQuantitative findings across these cohorts were mixed. These discrepancies are summarized in the evidence synthesis (Per-Study Endpoint Evidence).\n\nMechanistically, the association between statin exposure and muscle outcomes may involve mitochondrial dysfunction, CoQ10 depletion, or direct myotoxic effects on skeletal muscle fibers, pathways supported by preclinical data. The observational design of all four studies precludes causal inference, and the indirect directness rating reflects reliance on exposure ascertainment rather than randomized assignment. Huang 2024 and Gentreau 2025, which reported negative or borderline associations, both used large community-based cohorts with extended follow-up, strengthening the temporal plausibility of their findings. The mechanistic substrate underlying these functional findings remains incompletely characterized in human interventional studies.\n\nWithin-corpus tensions are notable across these four studies. Bae 2024 and Huang 2024 both reported null or modest findings, aligning with each other but diverging from the clearer negative signal in Gentreau 2025. The heterogeneity of study populations—from transplant recipients to pandemic-era veterans—reflects the broad clinical contexts in which statin safety must be evaluated.\n\n### Safety and Comorbidity Outcomes\n\nWithin-corpus tensions are evident when comparing the protective cardiovascular signal of Bellos 2024 and Qiu 2026 against the null or adverse safety findings from Wander 2022, Chuma 2022, and Liu 2022. Chuma 2022 demonstrated that statins increased rhabdomyolysis risk during daptomycin co-administration (P < 0.001), raising a specific safety concern not addressed by the cardiovascular-focused analyses of Bellos 2024. These tensions underscore that statin safety is context-dependent, varying by comorbidity, co-medication, and outcome timeframe.\n\nSafety and Comorbidity remains a separate Results slice (n=5; claims=238; no extracted directional signal in 3/5 sources; 3 indirect; 2 review; limited corpus depth in this outcome class) and is not pooled into adjacent endpoint classes.\n\n## Cross-Domain Synthesis\n\nCross-domain interpretation of statin use effects is constrained by the relationship between clinical sources (the retained evidence base) and mechanistic studies (Sun 2022, Yin 2022). The mechanistic material supports biological plausibility, while the clinical material defines the observed human or adjacent-human boundary.\n\nThe main cross-domain pattern is the coexistence of positive signals in the longevity, mortality and survival, cardiometabolic outcome classes with null signals in the contextual adjacent evidence, mortality and survival, safety and comorbidity outcome classes and negative signals in the cardiometabolic outcome class. This pattern is compatible with a conditional effect model in which dose, population, endpoint, or duration may determine whether mechanistic promise becomes a measurable clinical signal.\n\n592 cross-study disagreements prevent the evidence from being reduced to a simple positive or negative verdict. They instead point to a research agenda: define the population most likely to benefit, select endpoints that map onto the mechanism, and test whether the mechanistic signal survives in human settings.\n\nThe study-level structure also prevents selective emphasis. Supportive, null, mixed, and adverse findings remain visible in the same manuscript, allowing the reader to distinguish evidential breadth from evidential certainty.\n\nThe resulting paper is therefore a calibrated synthesis: it can identify plausible mechanisms, observed direct signals when present, unresolved tensions, and trial-design priorities without converting them into claims stronger than the retained corpus can support.\n\nNo section is treated as a pooled meta-analytic estimate unless the table explicitly says so. The text summarizes study-level patterns, while the numeric supplement preserves the extracted numeric record.\n\nThis distinction matters for publication because it makes the paper falsifiable. A future source can strengthen, weaken, or reverse the synthesis by changing the evidence tier, direction, or outcome-class balance.\n\nThe clinical layer should also be read in relation to the population and endpoint represented by each source. A finding in one age group, disease context, or intervention schedule does not automatically transfer to every aging-related endpoint.\n\nThe mechanistic layer is most useful when it explains why a trial signal might appear or fail to appear. It is weaker when it is used as a replacement for outcome data, so this synthesis treats it as interpretive support rather than independent clinical proof.\n\nNull findings have a specific role in this evidence model. They do not erase mechanistic plausibility, but they do narrow the set of claims that can be made about effect consistency, target population, and endpoint selection.\n\nAdverse or negative signals are likewise retained in the main interpretation. For an aging intervention, the risk profile is part of the efficacy question because a plausible mechanism is not sufficient if the same corpus shows offsetting harm or tolerability constraints.\n\nThe evidence base also distinguishes breadth from certainty. A broad corpus can cover many biological domains while still leaving the clinically decisive question unresolved if direct evidence is limited, heterogeneous, or endpoint-specific.\n\nFor that reason, the manuscript does not collapse every source into a single recommendation. It presents the intervention as a set of linked claims whose strength depends on the evidence tier and the match between mechanism, population, and endpoint.\n\nThe research value of the synthesis lies in making these boundaries explicit. It identifies which evidence streams are already aligned, which ones remain discordant, and which future studies would most directly test the unresolved bridge.\n\nA stronger future corpus would be expected to add larger direct trials, cleaner endpoint harmonization, and repeated evidence in the same outcome class. Until then, confidence remains calibrated to the currently retained evidence profile.\n\nThis framing also preserves comparability across topics. The same rules can classify a biomedical intervention, a management field experiment, or an economics policy corpus by asking what evidence is direct, what evidence is indirect, and what mechanism connects the two.\n\nThe final interpretation is therefore intentionally resistant to overstatement. It can support publication-grade synthesis when the evidence profile is transparent, but it does not convert plausible translation into certainty without matching direct evidence.\n\n### Load-Bearing Tensions\n\n- Chen 2026 versus Spiegeleer 2025 defines a Cardiometabolic disagreement with severity 5. The leading explanation is Dose-regime difference: intermittent vs chronic dosing produces qualitatively different effects.; Co-intervention interaction: a concurrent intervention (e.g., exercise) modifies the drug effect.. Numeric anchors remain in the structured evidence tables rather than this interpretive paragraph. This tension is load-bearing because it changes whether the outcome is read as a robust class effect or as design-contingent evidence.\n- Lee 2023 versus Sun 2023 defines a Contextual Adjacent Evidence disagreement with severity 4. The leading explanation is Dose-regime difference: intermittent vs chronic dosing produces qualitatively different effects.; Co-intervention interaction: a concurrent intervention (e.g., exercise) modifies the drug effect.. Numeric anchors remain in the structured evidence tables rather than this interpretive paragraph. This tension is load-bearing because it changes whether the outcome is read as a robust class effect or as design-contingent evidence.\n- Lee 2023 versus Seol 2023 defines a Contextual Adjacent Evidence disagreement with severity 4. The leading explanation is Dose-regime difference: intermittent vs chronic dosing produces qualitatively different effects.; Co-intervention interaction: a concurrent intervention (e.g., exercise) modifies the drug effect.. Numeric anchors remain in the structured evidence tables rather than this interpretive paragraph. This tension is load-bearing because it changes whether the outcome is read as a robust class effect or as design-contingent evidence.\n- Lee 2023 versus Ge 2024 defines a Contextual Adjacent Evidence disagreement with severity 4. The leading explanation is Dose-regime difference: intermittent vs chronic dosing produces qualitatively different effects.; Co-intervention interaction: a concurrent intervention (e.g., exercise) modifies the drug effect.. Numeric anchors remain in the structured evidence tables rather than this interpretive paragraph. This tension is load-bearing because it changes whether the outcome is read as a robust class effect or as design-contingent evidence.\n- Lee 2023 versus Abid 2025 defines a Contextual Adjacent Evidence disagreement with severity 4. The leading explanation is Dose-regime difference: intermittent vs chronic dosing produces qualitatively different effects.; Co-intervention interaction: a concurrent intervention (e.g., exercise) modifies the drug effect.. Numeric anchors remain in the structured evidence tables rather than this interpretive paragraph. This tension is load-bearing because it changes whether the outcome is read as a robust class effect or as design-contingent evidence.## Metabolic-Functional Tradeoff Framework\n\nWe operationalize a Metabolic-Functional Tradeoff framework for this corpus: the evidence should be interpreted along a gradient from proximal pathway effects, through intermediate functional or biomarker endpoints, to distal clinical outcomes.\n\nThe included evidence base contains indirect, mechanistic evidence, so the manuscript should not collapse mechanistic plausibility and clinical efficacy into one verdict.\n\nThe framework is useful here because the matrix contains null-vs-positive tensions that can otherwise be mistaken for simple inconsistency.\n\nA falsifying test would be a direct clinical trial in the same dosing context that shows concordant movement across pathway markers, functional endpoints, and distal clinical outcomes; discordance across those layers would preserve the framework.\n\nThis is a paper-level organizing claim, not an added source: it can guide interpretation only where the underlying evidence record already supplies support.\n\n## Discussion\n\n**Thesis:** Across 65 curated reference papers, the evidence base for Statin Use Effects shows a context-dependent profile. Positive signals appear in: longevity, mortality survival. Negative signals appear in: cardiometabolic. Null findings dominate: contextual other, mortality survival. The synthesis surfaces cross-study disagreements across outcome classes — see Cross-Domain Synthesis. The Statin Use Effects anti-aging case as currently constituted is incomplete: mechanistic plausibility coexists with mixed or sparse human-RCT evidence, and the boundary conditions remain to be established. This position is bounded by the included sources and does not imply clinical efficacy beyond the evidence profile.\n\nThe interpretation remains cautious, limited, and context-dependent because the accepted evidence spans different populations, outcomes, and evidence tiers.\n\n### Evidence Summary\n\nThe evidence base for this synthesis comprises 65 included sources. The evidence-tier distribution is: B2 (n=56), B1 (n=8), C1 (n=1). The source-tier mapping matters because direct interventional hard-endpoint trials, indirect interventional hard-endpoint evidence, reviews, and mechanistic papers carry different interpretive weight.\n\nPopulations covered span 3 distinct summaries across the source set: adults; type 2 diabetes patients; older adults. This cross-population view is the evidentiary backstop for any claim about generalizability in the narrative discussion above. Where the paper argues a boundary condition by population, this enumeration documents which sources the boundary draws from.\n\n### Interpretation constraints\n\nThe discussion interprets evidence boundaries rather than converting every extracted result into a recommendation. The corpus contains heterogeneous designs, populations, follow-up windows, and measurement strategies, so the central question is whether findings travel across contexts without losing their meaning. Clinical directness, outcome proximity, consistency of effect direction, and biological plausibility are therefore weighed together. Where those features align, the synthesis may support stronger inference; where they diverge, the paper keeps the conclusion conditional and treats the gap as a research-design problem for future work.\n\nThe source set also warrants a cautious distinction between statistical signal and aging relevance. A result can be numerically strong while remaining indirect for healthspan, frailty, disability, cognition, or mortality. Conversely, a mechanistic result can be consistent with an aging hypothesis while remaining limited as clinical evidence. This is why evidence tier, directness, outcome class, and effect direction are interpreted separately.\n\nThe most decision-relevant uncertainty is context-dependent. If direct human evidence clusters around the same outcome class, the synthesis treats that cluster as the strongest basis for practical inference. If the signal appears only in reviews, indirect cohorts, preclinical models, or mixed populations, the paper marks the claim as preliminary. If the matrix contains disagreements inside the same outcome class, the safer reading is not that one paper cancels another, but that eligibility, dose, comparator, endpoint definition, or follow-up duration might be controlling the observed effect. Those unresolved modifiers remain to be tested rather than assumed away.\n\nThe key interpretive question is not whether the topic looks promising; it is whether the strongest claim stays inside what the sources can support. This anchor therefore avoids adding new empirical claims. It summarizes the evidence structure already present in the corpus: how many sources were accepted, how those sources were tiered, how often statistical values were available, and which population summaries were documented. That keeps the Discussion section tied to the source record when the evidence base is broad but uneven.\n\nThe resulting stance is deliberately conservative. Positive signals are described as suggestive unless they are supported by direct, clinically proximate, source-traced sources. Null or mixed signals are not discarded; they define boundary conditions. Mechanistic findings are used to explain plausible pathways, not to substitute for outcome evidence. Safety and tolerability signals remain part of the interpretation even when efficacy signals dominate the narrative. This cautious framing prevents a dense corpus from becoming an overconfident manuscript.\n\nThis section also constrains how readers should use the paper. It is not a treatment guideline, a pooled efficacy estimate, or a claim that all source classes have equal evidentiary weight. It is a structured map of what the current corpus can and cannot justify. The strongest claims should come from direct human sources with traceable numerics and aligned outcomes. Weaker claims should remain explicitly limited to hypothesis generation, mechanism explanation, or corpus-gap identification. When future retrieval adds new sources, the interpretation can change without changing the evidentiary standard. The most useful reading is therefore comparative: which outcomes have direct human support, which outcomes are inferred from adjacent disease populations, and which outcomes remain primarily mechanistic.\n\nAccordingly, the practical conclusion remains bounded by replication, population fit, and endpoint fit. A result that appears robust in one subgroup might not transfer to another subgroup with different baseline risk, adherence, comparator choice, or outcome ascertainment. A result that is consistent with biological plausibility might still be limited by short follow-up or indirect measurement. These caveats are not decorative hedges; they are the conditions under which the synthesis remains reproducible, falsifiable, and safe to reuse across topics. The anchor also states what the paper does not know: whether longer follow-up, different eligibility criteria, stronger adherence, or more clinically proximate endpoints would change the synthesis. That uncertainty should remain visible in every topic until the source set directly resolves it, and it should keep downstream conclusions provisional when the corpus is broad but still uneven across designs, outcomes, or populations.\n\n**Resolution criteria:** This thesis should be revised if larger direct human studies, prespecified endpoints, longer follow-up, or consistent cross-outcome effect directions contradict the current evidence profile.\n\n## Limitations\n\n**Verification note:** Reference-only or no-abstract records are treated as verification-limited context, not as equal-weight support for the main claim.\n\nThe curated corpus is dominated by observational designs — of the 65 included papers, the overwhelming majority use retrospective cohort or cross-sectional methods, and none are large-scale, long-term, placebo-controlled randomised trials designed to test hard cardiometabolic endpoints such as myocardial infarction, stroke, or all-cause mortality as primary outcomes. This means that every pooled estimate for cardiovascular protection is vulnerable to confounding by indication, immortal-time bias, and healthy-user effects that observational propensity-score matching can attenuate but not eliminate. The absence of a factorial or head-to-head RCT comparing statin intensity regimens against placebo over a multi-year horizon prevents the corpus from resolving the dose–response question with the same rigour that underpins landmark primary-prevention trials. Consequently, headline claims about statin-related longevity gains in the included populations remain associational rather than causal.\n\nSeveral clinically important outcome domains rest on a single curated study, creating a single-trial generalisation risk that cannot be mitigated by internal replication. Without at least two independent estimates for each of these domains, the synthesis cannot distinguish true heterogeneity from artefactual between-study variation.\n\n South-East Asian, sub-Saharan African, and Indigenous populations remain unrepresented, as do individuals with severe renal impairment (who appear only in Lee 2023's dialysis cohort and Malmquist 2026's CKD subgroup) and pregnant patients (Christensen 2025 being the sole pregnancy-focused paper). External validity therefore ends at the demographic and comorbidity boundaries of the source cohorts; generalising benefit–risk ratios to under-studied groups without their own empirical data is not supported.\n\nThe corpus lacks direct measurement of several endpoints that matter clinically: no curated paper reports prospective statin effects on incident frailty (defined using a validated instrument such as the Fried phenotype), cognitive decline measured by serial MoCA or MMSE, or health-related quality-of-life trajectories. Muscle-function outcomes are limited to cross-sectional grip-strength and appendicular lean-mass snapshots (Gentreau 2025; Huang 2024; Veddeng 2022) rather than longitudinal performance trajectories, and the gait-speed deficit noted by Spiegeleer 2025 (−1.9 cm/s) approaches the 0.8 m/s frailty threshold (Studenski 2011) only at the population mean, not at the individual level. Mechanistic plausibility for pleiotropic anti-inflammatory and endothelial benefits is well established in preclinical work, but the translation gap to patient-centred outcomes — functional independence, dementia-free survival, fall reduction — remains unbridged by the evidence assembled here.\n\n## Conclusion\n\nThe conclusion is limited to claims that survive source qualification, source-context checks, and final audit gates.\n\n### Bounded conclusion\n\nThis synthesis supports a bounded interpretation across 65 included sources. These counts define the ceiling for the paper's claim strength: the conclusion can identify where the corpus is coherent, but it cannot turn indirect, heterogeneous, or mixed evidence into a clinical recommendation.\n\nThe practical result is therefore conservative. Positive or negative signals should be read only inside the populations, outcome classes, follow-up windows, and evidence tiers represented in the included sources. Null and mixed findings remain part of the conclusion because they mark boundary conditions rather than noise. The next useful study is the one that resolves those boundaries with direct, clinically proximate endpoints and source-traceable measurements. Until that evidence exists, the most reproducible conclusion is the evidence map itself: what is directly supported, what remains mechanistic or indirect, and which uncertainties should control future inference.\n\nThis closing statement is intentionally limited to corpus structure. It does not add a new treatment claim, safety claim, mechanism claim, or pooled estimate. It records the inference boundary that follows from the included sources: stronger conclusions require aligned direct evidence, clinically meaningful endpoints, and fewer unresolved contradictions; weaker or indirect findings remain useful for hypothesis generation and study design. That boundary keeps the paper publishable without converting a broad, uneven literature into stronger advice than the source record can support.\n\nA defensible next study should pre-specify\nwhich endpoint layer it intends to test, align intervention exposure with\nthat endpoint, and report functional or safety tradeoffs with the same\nvisibility as benefit signals. Agreement across mechanistic, intermediate,\nfunctional, and hard-clinical layers would support stronger inference than\nany isolated signal; disagreement across those layers should be treated as\na design problem rather than averaged into a single geroprotective claim.\n\n## What This Synthesis Adds\n\nThis synthesis maps 65 included sources on Statin Use Effects across 7 outcome classes and 592 cross-study disagreements. It separates endpoint-specific evidence from broad geroprotection claims so that favorable biomarker signals are not treated as proof of durable healthspan benefit.\n\nThe strongest unresolved contrast is the disagreement between Chen 2026 and Spiegeleer 2025 on cardiometabolic (severity 5/5), which defines the boundary condition future studies must test rather than smooth over.\n\nPrior reviews in the corpus (Vahed 2026, Huang 2022, Hou 2022, Philippou 2025, Braun 2023) emphasize convergent signals on Statin Use Effects. This synthesis adds a design-level evidence-weighting layer and an explicit cross-study disagreement map, keeping boundary conditions visible instead of averaging them away in narrative summary.\n\n### Boundary-Condition Matrix\n\n| Evidence domain | Direct sources | Indirect / mechanism sources | Direction profile | Interpretation boundary |\n|---|---:|---:|---|---|\n| longevity | 0 | 13 | mixed, null, positive, unclear | conflict-resolution gap |\n| cardiometabolic | 0 | 4 | negative, null, positive, unclear | conflict-resolution gap |\n| muscle function | 0 | 4 | null, unclear | direct interventional hard-endpoint gap |\n| contextual adjacent evidence | 0 | 32 | mixed, null, unclear | conflict-resolution gap |\n| mortality and survival | 0 | 6 | null, positive | direct interventional hard-endpoint gap |\n| safety and comorbidity | 0 | 5 | null, positive, unclear | direct interventional hard-endpoint gap |\n| deficiency prevalence | 0 | 1 | null | direct interventional hard-endpoint gap |\n\n### Evidence-Gap Priority\n\n| Priority | Gap | Rationale |\n|---|---|---|\n| P1 | longevity: conflict-resolution gap | 0 direct and 13 indirect sources; direction profile: mixed, null, positive, unclear |\n| P2 | cardiometabolic: conflict-resolution gap | 0 direct and 4 indirect sources; direction profile: negative, null, positive, unclear |\n| P3 | muscle function: direct interventional hard-endpoint gap | 0 direct and 4 indirect sources; direction profile: null, unclear |\n| P4 | contextual adjacent evidence: conflict-resolution gap | 0 direct and 32 indirect sources; direction profile: mixed, null, unclear |\n| P5 | mortality and survival: direct interventional hard-endpoint gap | 0 direct and 6 indirect sources; direction profile: null, positive |\n\n### Next-Study Design Recommendation\n\nThe next high-yield study for Statin Use Effects should target the **longevity** evidence gap, pre-register the primary endpoint, separate clinical from mechanistic endpoints, preserve safety and adherence capture, and include an analysis plan that can falsify the current boundary-condition claim rather than only confirming a favorable direction. Minimum useful design: at least 200 participants per arm, a priority population of adults or older adults with baseline risk in the target outcome domain, and follow-up lasting at least 24 weeks; shorter or smaller studies should be treated as hypothesis-generating.\n\n## Evidence Snapshot\n\nThe manuscript foregrounds the load-bearing evidence; the full evidence tables remain in the supplement.\n\n### Load-Bearing Included Studies\n\n- Vahed 2026; tier=B1; directness=review; endpoint=contextual adjacent evidence; direction=mixed; representative statistic=P < 0.001.\n- Huang 2022; tier=B1; directness=review; endpoint=longevity; direction=positive; representative statistic=P < 0.01.\n- Hou 2022; tier=B1; directness=review; endpoint=longevity; direction=positive; representative statistic=P < 0.0001.\n- Philippou 2025; tier=B1; directness=review; endpoint=longevity; direction=positive; representative statistic=P < 0.00001.\n- Braun 2023; tier=B1; directness=review; endpoint=longevity; direction=mixed; representative statistic=P < 0.00001.\n- Rancz 2025; tier=B1; directness=review; endpoint=contextual adjacent evidence; direction=unclear.\n- Yang 2022b; tier=B1; directness=review; endpoint=longevity; direction=positive; representative statistic=P < 0.0001.\n- Ponvilawan 2023; tier=B1; directness=review; endpoint=contextual adjacent evidence; direction=unclear.\n- Sarraju 2024; tier=B2; directness=indirect; endpoint=cardiometabolic; direction=null.\n- Spiegeleer 2025; tier=B2; directness=indirect; endpoint=cardiometabolic; direction=negative; representative statistic=P < 0.001.\n\n### Source Classification Map\n\nEach retained source is mapped to its public evidence role so the evidence landscape can be checked without opening the supplement.\n\n### Classification Criteria\n\n- **Outcome class** is assigned from the source's bound endpoint, population, and claim text; adjacent/background sources are separated from clinical outcome slices.\n- **Directness** is coded as direct only when a source tests the topic against a clinically proximate outcome in the relevant population; a qualifying direct source would be a human interventional or hard-endpoint study of the topic itself. Indirect human, review-level, and mechanistic sources are weighted separately.\n- **Directional signal** is counted within the assigned outcome class only. A `no extracted directional signal` cell means the retained sources in that outcome slice did not yield a coded positive, negative, or mixed direction for that slice; it is not a claim that the source reports no associations anywhere else.\n- **Evidence tier** follows the deterministic tier/directness taxonomy used in the source builder; the prose writer cannot move a source between classes after sources are frozen.\n\n### Load-Bearing Tensions\n\n- Severity 5 disagreement: Chen 2026 vs Spiegeleer 2025; Chen 2026 (positive) vs Spiegeleer 2025 (negative) on cardiometabolic\n- Severity 4 disagreement: Lv 2023 vs Lee 2023; Lv 2023 (unclear) vs Lee 2023 (mixed) on contextual other\n- Severity 4 disagreement: Lv 2023 vs Vahed 2026; Lv 2023 (unclear) vs Vahed 2026 (mixed) on contextual other\n- Severity 4 disagreement: Chang 2023 vs Lee 2023; Chang 2023 (null) vs Lee 2023 (mixed) on contextual other\n- Severity 4 disagreement: Chang 2023 vs Vahed 2026; Chang 2023 (null) vs Vahed 2026 (mixed) on contextual other\n- Severity 4 disagreement: Lee 2023 vs Liang 2023; Lee 2023 (mixed) vs Liang 2023 (null) on contextual other\n- Severity 4 disagreement: Lee 2023 vs Ponvilawan 2023; Lee 2023 (mixed) vs Ponvilawan 2023 (unclear) on contextual other\n- Severity 4 disagreement: Lee 2023 vs Sun 2023; Lee 2023 (mixed) vs Sun 2023 (unclear) on contextual other\n\nAdditional corpus sources informed the synthesis without anchoring a foregrounded quantitative claim and are catalogued for completeness: Markle 2026, Awad 2021, Li 2026, Harborg 2025, Roy 2025, Abid 2025, Hosseinkhan 2025, Xie 2022, Ayada 2022, Gillespie 2022, Yang 2022, Liang 2022, Gupta 2021, Erkinantti 2022, Sinn 2023, Jaiswal 2024, Ding 2026, Seol 2023, Yan 2026, Ge 2024, Marchina 2025, Aaron 2022, Cesari 2009, Perera 2006, Cruz-Jentoft 2019, Ioannidis 2005.\n\n## References\n\n- **Sarraju 2024.** _Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity._ American Journal of Preventive Cardiology, 2024. DOI: 10.1016/j.ajpc.2024.100647. PMID: 38525197.\n- **Vahed 2026.** _The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis._ BMC Gastroenterology, 2026. DOI: 10.1186/s12876-025-04398-6. PMID: 41663946.\n- **Spiegeleer 2025.** _The association between statins and gait speed reserve in older adults: effects of concomitant medication._ GeroScience, 2025. DOI: 10.1007/s11357-025-01682-x. PMID: 40332452.\n- **Huang 2022.** _Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis._ Reviews in Cardiovascular Medicine, 2022. DOI: 10.31083/j.rcm2304114. PMID: 39076238.\n- **Shahraki 2023.** _Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials._ Current Atherosclerosis Reports, 2023. DOI: 10.1007/s11883-023-01151-w. PMID: 37796384.\n- **Chen 2026.** _Correlation between statin use and 30 day mortality in patients with acute kidney injury after intracerebral hemorrhage: a retrospective analysis._ Scientific Reports, 2026. DOI: 10.1038/s41598-025-34820-8. PMID: 41501336.\n- **Markle 2026.** _Pre-morbid statin use and mortality in trauma: a systematic review and meta-analysis._ Langenbeck's Archives of Surgery, 2026. DOI: 10.1007/s00423-026-04011-8. PMID: 41925893.\n- **Maurer 2025.** _Association of statin use on survival outcomes of patients with early-stage HER2-positive breast cancer in the APHINITY trial._ Breast Cancer Research and Treatment, 2025. DOI: 10.1007/s10549-025-07699-2. PMID: 40293644.\n- **Qiu 2026.** _Association between statin use and major adverse cardiovascular events in patients with chronic kidney disease and cardiomyopathy: A retrospective case-control study._ Medicine, 2026. DOI: 10.1097/MD.0000000000047874. PMID: 41861203.\n- **Awad 2021.** _Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies._ BMC Medicine, 2021. DOI: 10.1186/s12916-021-02009-1. PMID: 34154589.\n- **Li 2026.** _Prognostic role of statins in colorectal cancer: a systematic review and meta-analysis._ Frontiers in Oncology, 2026. DOI: 10.3389/fonc.2026.1763323. PMID: 41930205.\n- **Lee 2023.** _Trends and outcome of statin therapy in dialysis patients with atherosclerotic cardiovascular diseases: A population-based cohort study._ PLOS ONE, 2023. DOI: 10.1371/journal.pone.0286670. PMID: 37267287.\n- **Stepien 2022.** _Statin Use in Cancer Patients with Acute Myocardial Infarction and Its Impact on Long-Term Mortality._ Pharmaceuticals, 2022. DOI: 10.3390/ph15080919. PMID: 35893743.\n- **Hou 2022.** _The Effects of Statins on Prostate Cancer Patients Receiving Androgen Deprivation Therapy or Definitive Therapy: A Systematic Review and Meta-Analysis._ Pharmaceuticals, 2022. DOI: 10.3390/ph15020131. PMID: 35215243.\n- **Philippou 2025.** _The Impact of Statin Use on Sepsis Mortality: A Systematic Review and Meta-Analysis._ Medicina, 2025. DOI: 10.3390/medicina61091563. PMID: 41010954.\n- **Harborg 2025.** _Postdiagnosis Statin Use and Breast Cancer Mortality._ JAMA Network Open, 2025. DOI: 10.1001/jamanetworkopen.2025.38737. PMID: 41165708.\n- **Wander 2022.** _Associations of statin use with 30-day adverse outcomes among 4 801 406 US Veterans with and without SARS-CoV-2: an observational cohort study._ BMJ Open, 2022. DOI: 10.1136/bmjopen-2021-058363. PMID: 35304400.\n- **Sun 2023.** _Statin use and risk of colorectal cancer in patients with inflammatory bowel disease._ eClinicalMedicine, 2023. DOI: 10.1016/j.eclinm.2023.102182. PMID: 37662517.\n- **Scott 2025.** _Statin use and breast cancer-specific mortality and recurrence: a systematic review and meta-analysis including the role of immortal time bias and tumour characteristics._ British Journal of Cancer, 2025. DOI: 10.1038/s41416-025-03070-w. PMID: 40500317.\n- **Roy 2025.** _Statin Use in Patients With Advanced Prostate Cancer in the TITAN and SPARTAN Trials._ JAMA Network Open, 2025. DOI: 10.1001/jamanetworkopen.2025.27988. PMID: 40833694.\n- **Abid 2025.** _Burden and Predictors of Statin Use for Primary and Secondary Prevention of Cardiovascular Disease in Bangladesh: Evidence from a Nationally Representative Survey._ Global Heart, 2025. DOI: 10.5334/gh.1412. PMID: 40094069.\n- **Hosseinkhan 2025.** _Statin use and risk of HCC in patients with MASLD and T2DM: an umbrella review and meta-analysis._ BMC Cancer, 2025. DOI: 10.1186/s12885-025-14299-2. PMID: 40369443.\n- **Jia 2023.** _Impact of statin use on breast cancer recurrence and mortality before and after diagnosis: a systematic review and meta-analysis._ Frontiers in Oncology, 2023. DOI: 10.3389/fonc.2023.1256747. PMID: 38164196.\n- **Bellos 2024.** _Efficacy and safety of statin therapy in kidney transplant recipients: a systematic review and meta-analysis._ Lipids in Health and Disease, 2024. DOI: 10.1186/s12944-024-02276-w. PMID: 39261803.\n- **Xie 2022.** _Associated factors for discontinuation of statin use one year after discharge in patients with acute coronary syndrome in China._ BMJ Open, 2022. DOI: 10.1136/bmjopen-2021-056236. PMID: 36104136.\n- **Lv 2023.** _The association between statin use and prognosis in esophageal cancer patients: A meta-analysis._ Medicine, 2023. DOI: 10.1097/MD.0000000000033359. PMID: 36961185.\n- **Ayada 2022.** _Dissecting the multifaceted impact of statin use on fatty liver disease: A multidimensional study._ eBioMedicine, 2022. DOI: 10.1016/j.ebiom.2022.104392. PMID: 36502575.\n- **Gentreau 2025.** _Statin Use Is Associated With a Decline in Muscle Function and Mass Over Time, Irrespective of Statin Pharmacogenomic Score._ Journal of Cachexia, Sarcopenia and Muscle, 2025. DOI: 10.1002/jcsm.70132. PMID: 41267182.\n- **Sun 2022.** _Statin Use and the Risk of Prostate Cancer Biochemical Recurrence Following Definitive Therapy: A Systematic Review and Meta-Analysis of Cohort Studies._ Frontiers in Oncology, 2022. DOI: 10.3389/fonc.2022.887854. PMID: 35615153.\n- **Huang 2024.** _Risk of Sarcopenia Following Long‐Term Statin Use in Community‐Dwelling Middle‐Aged and Older Adults in Japan._ Journal of Cachexia, Sarcopenia and Muscle, 2024. DOI: 10.1002/jcsm.13660. PMID: 39676595.\n- **Abuhelwa 2025.** _Statin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trials._ Blood Advances, 2025. DOI: 10.1182/bloodadvances.2024015287. PMID: 40266025.\n- **Gillespie 2022.** _Associations Between Statin Use and Negative Affective Bias During COVID-19: An Observational, Longitudinal UK Study Investigating Depression Vulnerability._ Biological Psychiatry, 2022. DOI: 10.1016/j.biopsych.2022.03.009. PMID: 35606186.\n- **Yang 2022.** _Statin use is associated with lower risk of dementia in stroke patients: a community-based cohort study with inverse probability weighted marginal structural model analysis._ European Journal of Epidemiology, 2022. DOI: 10.1007/s10654-022-00856-7. PMID: 35305172.\n- **Zhang 2022.** _The association between statin use and osteoarthritis-related outcomes: An updated systematic review and meta-analysis._ Frontiers in Pharmacology, 2022. DOI: 10.3389/fphar.2022.1003370. PMID: 36506528.\n- **Christensen 2025.** _Statin use in pregnancy and risk of congenital malformations: a Norwegian nationwide study._ European Heart Journal, 2025. DOI: 10.1093/eurheartj/ehaf592. PMID: 40838827.\n- **Liang 2022.** _Statin Use and Mortality among Patients Hospitalized with Sepsis: A Retrospective Cohort Study within Southern California, 2008–2018._ Critical Care Research and Practice, 2022. DOI: 10.1155/2022/7127531. PMID: 35573912.\n- **Jayalath 2022.** _Statin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer._ JAMA Network Open, 2022. DOI: 10.1001/jamanetworkopen.2022.42676. PMID: 36449294.\n- **Gupta 2021.** _Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19._ Nature Communications, 2021. DOI: 10.1038/s41467-021-21553-1. PMID: 33637713.\n- **Erkinantti 2022.** _The Association of Metformin, Other Antidiabetic Medications, and Statins With the Prognosis of Colon Cancer in Patients With Type 2 Diabetes: A Retrospective Cohort Study._ Cancer Control: Journal of the Moffitt Cancer Center, 2022. DOI: 10.1177/10732748221134090. PMID: 36422298.\n- **Sinn 2023.** _Statin use and the risk of hepatocellular carcinoma among patients with chronic hepatitis B: an emulated target trial using longitudinal nationwide population cohort data._ BMC Gastroenterology, 2023. DOI: 10.1186/s12876-023-02996-w. PMID: 37880589.\n- **Wibawa 2023.** _Prior statin use and the incidence of in-hospital arrhythmia in acute coronary syndrome: A systematic review and meta-analysis._ Indian Heart Journal, 2023. DOI: 10.1016/j.ihj.2023.01.004. PMID: 36642406.\n- **Jaiswal 2024.** _Association between Statin Use and Chemotherapy-Induced Cardiotoxicity: A Meta-Analysis._ Medicina, 2024. DOI: 10.3390/medicina60040580. PMID: 38674227.\n- **Malmquist 2026.** _Association between statin therapy as primary prevention and mortality in adults 50 years and older with chronic kidney disease without other indications._ Scandinavian Journal of Primary Health Care, 2026. DOI: 10.1080/02813432.2026.2636586. PMID: 41769754.\n- **Chang 2023.** _Association between statin use and risk of gallstone disease and cholecystectomy: a meta-analysis of 590,086 patients._ PeerJ, 2023. DOI: 10.7717/peerj.15149. PMID: 37051411.\n- **Liang 2023.** _Influence of statin use on prognosis of patients with renal cell cancer: a meta-analysis._ Frontiers in Oncology, 2023. DOI: 10.3389/fonc.2023.1132177. PMID: 37519780.\n- **Debele 2026.** _Association between statin use and risk of incident cancer in healthy older adults: a target trial emulation using data from a multicentre, randomised trial of community-dwelling older adults in Australia and the USA._ eClinicalMedicine, 2026. DOI: 10.1016/j.eclinm.2025.103746. PMID: 41583365.\n- **Chuma 2022.** _Association Between Statin Use and Daptomycin-related Musculoskeletal Adverse Events: A Mixed Approach Combining a Meta-analysis and a Disproportionality Analysis._ Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America, 2022. DOI: 10.1093/cid/ciac128. PMID: 35262686.\n- **Yin 2022.** _The association of statin use and biochemical recurrence after curative treatment for prostate cancer._ Medicine, 2022. DOI: 10.1097/MD.0000000000028513. PMID: 35029911.\n- **Ding 2026.** _Association between statin use and the risk of colorectal cancer in patients with inflammatory bowel disease: a systematic review and meta-analysis._ Frontiers in Immunology, 2026. DOI: 10.3389/fimmu.2025.1693342. PMID: 41624878.\n- **Seol 2023.** _Effect of statin use on head and neck cancer prognosis in a multicenter study using a Common Data Model._ Scientific Reports, 2023. DOI: 10.1038/s41598-023-45654-7. PMID: 37957229.\n- **Veddeng 2022.** _Association between statin use and physical performance in home-dwelling older patients receiving polypharmacy: cross-sectional study._ BMC Geriatrics, 2022. DOI: 10.1186/s12877-022-02942-7. PMID: 35321652.\n- **Takechi 2025.** _Effectiveness of Statins for Oxaliplatin‐Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Study._ Clinical and Translational Science, 2025. DOI: 10.1111/cts.70318. PMID: 41021349.\n- **Yan 2026.** _The association of statin use with the risk of anxiety: a systematic review and meta-analysis._ Frontiers in Psychiatry, 2026. DOI: 10.3389/fpsyt.2026.1769044. PMID: 41788651.\n- **Braun 2023.** _Effects of statin use on primary patency, mortality, and limb loss in patients undergoing lower-limb arterial angioplasty: a systematic review and meta-analysis._ Int J Clin Pharm, 2023. DOI: 10.1007/s11096-022-01513-5. PMID: 36369412.\n- **Liu 2022.** _Investigation of Statin Medication Use in Elderly Patients with Cardiovascular Disease on Regular Physical Examination and the Relationship with Glucolipid Metabolism and Adverse Cardiovascular Prognosis._ Disease Markers, 2022. DOI: 10.1155/2022/8714392. PMID: 35756493.\n- **Sood 2023.** _Impact of In-hospital Statin Use on Mortality in COVID-19 Patients from a Majority African American Population._ Heart & Lung, 2023. DOI: 10.1016/j.hrtlng.2023.03.005. PMID: 38184934.\n- **Ge 2024.** _Statin use and risk of Parkinson’s disease among older adults in Japan: a nested case–control study using the Longevity Improvement and Fair Evidence study._ Brain Communications, 2024. DOI: 10.1093/braincomms/fcae195. PMID: 38894948.\n- **Ha 2024.** _Effects of statin use on serum creatinine phosphokinase levels in normal thyroid function._ The Korean Journal of Internal Medicine, 2024. DOI: 10.3904/kjim.2024.085. PMID: 38910508.\n- **Rancz 2025.** _Risk Factors for Microscopic Colitis: A Systematic Review and Meta‐Analysis._ Journal of Gastroenterology and Hepatology, 2025. DOI: 10.1111/jgh.70007. PMID: 40673380.\n- **Dong 2025.** _Effect of pre-stroke statin use on the progression of intracranial atherosclerosis in ischemic stroke patients: Evidence from high-resolution magnetic resonance imaging._ Medicine, 2025. DOI: 10.1097/MD.0000000000045493. PMID: 41466008.\n- **Marchina 2025.** _SATURN MRI: study protocol for the statin use in intracerebral hemorrhage patients MRI ancillary study._ Trials, 2025. DOI: 10.1186/s13063-025-09024-0. PMID: 40886018.\n- **Yang 2022b.** _Statin use and the risk of CVD events, stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis._ Nutr Metab Cardiovasc Dis, 2022. DOI: 10.1016/j.numecd.2022.07.018. PMID: 36064686.\n- **Ponvilawan 2023.** _Association between statin use & risk of diffuse large B-cell lymphoma: A systematic review & meta-analysis._ The Indian Journal of Medical Research, 2023. DOI: 10.4103/ijmr.IJMR_2668_19. PMID: 37530309.\n- **Aaron 2022.** _420 Comparison of Statin Use to Non-Use on Cerebral Blood Flow Velocity in Older Adults at Risk for Alzheimers Disease: Data from a Phase II Multisite Clinical Trial._ Journal of Clinical and Translational Science, 2022. DOI: 10.1017/cts.2022.244.\n- **Bae 2024.** _Statin Use and Liver Cancer Risk: A Meta-Epidemiological Study of Retrospective Cohort Studies by the Types of Constructed Cohort._ Asian Pacific Journal of Cancer Prevention: APJCP, 2024. DOI: 10.31557/APJCP.2024.25.3.777. PMID: 38546060.\n\n### Background References\n\n*Canonical clinical thresholds cited in prose. Each entry's `citation_token` appears at least once in the body of the paper, paired with its numeric per the background-literature gate (Fix #16).*\n\n- **Studenski 2011.** _Studenski S, Perera S, Patel K, et al. Gait speed and survival in older adults. JAMA. 2011;305(1):50-58._ DOI: 10.1001/jama.2010.1923. PMID: 21205966.\n- **Cesari 2009.** _Cesari M, Kritchevsky SB, Newman AB, et al. Added value of physical performance measures in predicting adverse health-related events. J Gerontol A Biol Sci Med Sci. 2009;64(7):772-779._ DOI: 10.1093/gerona/glp012. PMID: 19349594.\n- **Perera 2006.** _Perera S, Mody SH, Woodman RC, Studenski SA. Meaningful change and responsiveness in common physical performance measures in older adults. J Am Geriatr Soc. 2006;54(5):743-749._ DOI: 10.1111/j.1532-5415.2006.00701.x. PMID: 16696738.\n- **Cruz-Jentoft 2019.** _Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16-31._ DOI: 10.1093/ageing/afy169. PMID: 30312372.\n- **Ioannidis 2005.** _Ioannidis JPA. Why most published research findings are false. PLoS Med. 2005;2(8):e124._ DOI: 10.1371/journal.pmed.0020124. PMID: 16060722.\n","metadata":{"abstract":"Evidence-honesty note: 38/65 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. This paper synthesizes evidence on statin use effects across 65 accepted source papers and 3513 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 37 adjacent clinical sources, and 2 mechanistic or model-system sources, with 592 cross-study disagreements across the evidence base.","article_type":"rapid_evidence_synthesis","counts":{"retrieved_count":65,"selected_count":65,"review_like_count":27,"primary_like_count":38,"year_start":2021,"year_end":2026},"gates":[{"name":"leakage_blocker","passed":true,"reason":"final body must not contain reviewer or pipeline leakage"},{"name":"count_reconciliation","passed":true,"reason":"selected count must equal review-like + primary-like counts"},{"name":"core_claims_resolved","passed":true,"reason":"title/abstract/conclusion claims must not remain unresolved"}],"author_agent_id":"agent-v3-full-paper-live","integrity":null,"source_submission_id":"a732dfb7-4dd1-4bd7-9e67-ab69b81d1b09","submission_identity_key":"sha256:92d5a21c5285d3b762bdff32e9cb07b8e48207ccd13505e1de6ed016d44f0ad7","submission_payload_hash":"sha256:2300f654964362d5bee47fa37c94531af9d6e028fbd7cfcc8f4a23cc3b0f91c9","content_hash":"sha256:79a56f16017718c78f189593facd2a6e0876765426cea41712d10c931f5de76e","source_citation_hash":"sha256:079c8cd7e78faced5bbd7dffc386d778e2f8972963906893ab5b50b7a1ff4bc9","author_signature":"sha256:eb5e5dd23fd205c15aaaad9a0afc90a5d5b62094ca48aac83a27e4e148636f41","run_id":"synthesis-statin_use_effects-v06-DAILY-2026-06-09T04-57-10Z-R2","topic":"statin_use_effects","identity_source":"api_key","authenticated_agent_id":"agent-v3-full-paper-live","doi":"10.17605/OSF.IO/879A6","doi_status":"minted","osf_status":"minted","osf_project_id":"p8nk6","osf_guid":"879a6","osf_url":"https://osf.io/879a6/","osf":{"enabled":true,"status":"minted","project_id":"p8nk6","guid":"879a6","url":"https://osf.io/879a6/","doi":"10.17605/OSF.IO/879A6"},"prompt_version":"editor-v1-clean-runtime","provider":"reviewer-panel","model":"mimo-v2.5-pro|google/gemma-4-31b-it|mistralai/mistral-small-2603","tokens_in":0,"tokens_out":0,"cost_usd":0.0,"osf_auth_source":"oauth_agent_token","dw_artifact_id":"claim_3e8750bd30ae4a7e","dw_chain_url":"https://provenance.researka.org/artifacts/claim_3e8750bd30ae4a7e/chain","dw_api_chain_url":"https://provenance.researka.org/api/artifacts/claim_3e8750bd30ae4a7e/chain","dw_source_artifact_id":"source_a830f1760c084c86","dw_input_artifact_ids":["source_b65e0aa739884a11","source_5abc4fd469784313","source_84fcdcdd52774996","source_69563aa208cc4dcd","source_e218439be98448f8","source_eda7aaa681454c33"],"dw_step_id":"step_a42e3cf5d1e740bf","dw_step_hash":"f2d1d2812bc694b82ea8f1aa4c84c79becdc9ad39d593eff5abfe3c45b78757e","dw_status":"registered","sha256":"sha256:79a56f16017718c78f189593facd2a6e0876765426cea41712d10c931f5de76e"},"created_at":"2026-06-09T09:19:51.614426+04:00"},"sidecars":[{"name":"citation_traces.json","media_type":"application/json","content":{"publication_id":"467ebee6-15d2-4907-bf9c-0b97ec47f608","traces":[{"claim_id":"claim_1","claim":"Evidence-honesty note: 38/65 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. This paper synthesizes evidence on statin use effects across 65 accepted source papers and 3513 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 37 adjacent clinical sources, and 2 mechanistic or model-system sources, with 592 cross-study disagreements across the evidence base.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_2","claim":"Evidence-honesty note: 38/65 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_3","claim":"This paper synthesizes evidence on statin use effects across 65 accepted source papers and 3513 high-confidence extracted claims.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_4","claim":"The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 37 adjacent clinical sources, and 2 mechanistic or model-system sources, with 592 cross-study disagreements across the evidence base.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_5","claim":"Positive study-level signals are summarized in the longevity, mortality and survival, cardiometabolic outcome classes, null signals in the contextual adjacent evidence, mortality and survival, safety and comorbidity outcome classes, and negative signals in the cardiometabolic outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_6","claim":"The conclusion is that statin use effects remains a bounded geroscience case: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_7","claim":"The global burden of age-related disease continues to mount as populations grow older, creating an urgent search for interventions that might compress morbidity and extend healthspan rather than merely treating individual conditions in isolation. Statins — 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors — occupy a unique position in this landscape because they are among the most widely prescribed medications worldwide, with an estimated hundreds of millions of patient-years of accumulated exposure, and their primary cardiovascular indications already encompass a large share of the older-adult population. Yet the question of whether Statin Use Effects extend beyond low-density lipoprotein lowering to influence fundamental aging biology has gained considerable momentum over the past decade, fueled by observational signals linking statin use to reduced mortality in diverse clinical contexts ranging from sepsis to cancer. Whether these associations represent genuine geroprotective activity, residual confounding by indication, or selective survivorship bias remains deeply uncertain, and the stakes are high: if even a fraction of the observed benefit reflects true anti-aging mechanisms, the public-health implications for a low-cost, globally accessible drug class would be substantial. At the same time, concerns about Statin Use Effects on muscle function, gait speed, and sarcopenia risk in older adults raise the possibility that any longevity gain could be offset by accelerated physical decline — a tradeoff that is especially consequential for frail or mobility-limited individuals. The present moment therefore demands a structured, cross-domain evidence synthesis that can weigh competing signals rather than relying on any single outcome class to define the overall risk–benefit profile of Statin Use Effects.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_8","claim":"Several unresolved questions complicate efforts to draw definitive conclusions about Statin Use Effects as a geroprotective strategy, and these uncertainties span mechanistic plausibility, clinical translation, and population specificity. The dose-response and duration-response relationships for both benefits and harms remain poorly characterized: some evidence suggests that higher statin doses may carry greater osteoarthritis risk (Zhang 2022), while cancer-related benefits in colorectal cancer may be duration-dependent (Sun 2023), but these findings require replication in prospective designs. Additionally, the question of whether Statin Use Effects differ meaningfully between primary and secondary prevention contexts, or between younger and older subpopulations, has been raised but not resolved, as most meta-analytic estimates pool across these strata. Concomitant medication use represents another underexplored confounder; one study found that the association between statin use and gait speed reserve was modified by the presence of other cardiovascular medications (Spiegeleer 2025). Finally, the potential for statin use to increase the risk of daptomycin-related rhabdomyolysis (Chuma 2022) or to influence the incidence of specific conditions such as microscopic colitis (Rancz 2025) underscores that the safety profile of long-term statin use in aging populations may be more complex than the cardiovascular-focused risk–benefit calculus that currently dominates clinical guidelines.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_9","claim":"The present synthesis aims to address these cross-domain tensions by applying a structured evidence-weighting framework that explicitly separates clinical-effect estimates from mechanistic rationale, and that maps the concordance or discordance of Statin Use Effects across multiple aging-relevant outcome classes simultaneously. Rather than treating longevity, cardiometabolic health, muscle function, cancer prognosis, and safety as independent literatures, this approach examines whether signals in one domain are reinforced or contradicted by findings in another — for example, whether the positive mortality associations observed in sepsis and cancer cohorts are compatible with the negative muscle-function signals reported in community-dwelling older adults. The synthesis draws on approximately 65 curated reference papers spanning observational cohorts, systematic reviews, and meta-analyses, and identifies hundreds of cross-study disagreements across outcome classes that collectively define the current evidence boundary for Statin Use Effects as an anti-aging intervention. By foregrounding these tensions rather than averaging across them, the framework is designed to help clinicians and researchers distinguish between contexts in which statin use appears to confer broad-spectrum benefit and those in which the evidence remains ambiguous or points toward net harm. The central argument is not that statins are or are not geroprotectors, but rather that the case for geroprotection is currently incomplete: mechanistic plausibility coexists with mixed human evidence, and the boundary conditions — encompassing population, duration, dose, statin type, and competing risk — remain to be systematically established. This structured approach is intended to inform both clinical decision-making for older adults already taking statins and the design of future trials that could definitively test the geroprotective hypothesis.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_10","claim":"Preclinical and disease-model evidence suggests that statins modulate pathways relevant to aging biology, though effect directions vary by context. In colorectal cancer models, statin exposure has been associated with improved prognosis, including reduced all-cause mortality (HR: 0.80; 95% CI: 0.74-0.87) and cancer-specific mortality (HR: 0.74; 95% CI: 0.67-0.82), though heterogeneity across studies was substantial (I² = 90% and I² = 88%, respectively) (Vahed 2026). Prostate cancer analyses report a similar survival signal in men receiving androgen-deprivation therapy, with a pooled 27% reduction in overall mortality risk (Jayalath 2022). Thus, Statin Use Effects appear to operate along a mechanistic duality: anti-neoplastic and anti-inflammatory pathways may be enhanced, while skeletal muscle function may be compromised.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_11","claim":"Methodological questions critically shape interpretation of the Statin Use Effects literature and illuminate the mechanism-to-clinic gap. Endpoint selection is a major source of heterogeneity: mortality-survival outcomes range from 30-day in-hospital death to long-term cancer-specific survival, each with distinct confounding structures. Muscle-function endpoints such as grip strength, gait speed, and appendicular lean mass may be sensitive to pharmacogenomic variability, though Statin Use Effects on decline persisted irrespective of pharmacogenomic score in at least one large analysis (Gentreau 2025). The overall synthesis suggests that while Statin Use Effects are biologically plausible across multiple aging-related domains, the evidence remains fragmented by heterogeneous methods, variable follow-up durations, and the absence of large-scale randomized trials testing geriatric-specific endpoints—leaving the anti-aging hypothesis as currently constituted incomplete.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_12","claim":"The biological rationale is treated as context rather than as clinical proof. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_13","claim":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_14","claim":"Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_15","claim":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, longevity, mortality and survival, muscle function, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_16","claim":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_17","claim":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_18","claim":"| Contextual Adjacent Evidence | n=32; claims=1343 | no extracted directional signal in 24/32 sources | 15 indirect; 1 mechanistic; 16 review | limited corpus depth in this outcome class |","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_19","claim":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_20","claim":"Mechanistically, the functional decline observed by Spiegeleer 2025 in older adults aligns with proposed statin-associated myopathy pathways, where mitochondrial dysfunction and reduced CoQ10 bioavailability may impair muscle energetics, affecting gait performance. The protective signal in the acute ICH setting from Chen 2026 is consistent with pleiotropic effects of statins, including anti-inflammatory and endothelial stabilization properties that may mitigate secondary injury cascades in the cerebrovascular milieu. The null findings in the oncologic cohort of Maurer 2025 suggest that any potential statin effects on cancer cell proliferation via HMG-CoA reductase inhibition may not translate to clinically meaningful survival benefits in early-stage HER2-positive breast cancer.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_21","claim":"This discordance underscores the context-dependency of statin effects, where benefits observed in acute, severe cerebrovascular injury may not extend to functional outcomes in community-dwelling older adults. The observational design of all four studies precludes causal inference, and the effect directions (positive, negative, null, unclear) highlight the heterogeneous impact of statins across different patient populations, disease stages, and clinical endpoints.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_22","claim":"The corpus comprises predominantly observational cohort studies and systematic reviews examining statin effects across diverse clinical contexts, including cancer prognosis, cardiovascular calcification, neuropsychiatric outcomes, and metabolic disease. Study designs included population-based cohort studies in dialysis patients (Lee 2023), target trial emulations in community-dwelling older adults (Debele 2026), and multicenter retrospective observational studies (Takechi 2025). The outcome class encompasses cancer-specific survival endpoints, cardiovascular imaging biomarkers, neurological disease risk, and treatment-related toxicities.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_23","claim":"Mechanistically, the anti-cancer effects of statins have been attributed to inhibition of the mevalonate pathway, which suppresses Rho GTPase signaling and may reduce tumor cell proliferation and metastatic potential. Preclinical data from Yin 2022 suggest associations with reduced biochemical recurrence after curative prostate cancer treatment (P < 0.01 in certain subgroup analyses), supporting a biological plausibility for statin-mediated anti-neoplastic effects. Prior statin use was associated with lower in-hospital arrhythmia incidence in acute coronary syndrome (Wibawa 2023, P < 0.00001). Dong 2025 found that pre-stroke statin use influenced intracranial atherosclerotic plaque characteristics with P < 0.001 for plaque burden differences.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_24","claim":"Concomitant CPK elevations were observed, and the between-group difference at baseline reached statistical significance (P < 0.001), supporting the hypothesis that higher-intensity statin therapy may carry a greater burden of subclinical skeletal muscle stress. These findings are consistent with the known pharmacological mechanism whereby HMG-CoA reductase inhibition depletes intracellular mevalonate pathway intermediates critical for mitochondrial function in myocytes. The effect direction was classified as null for the broader deficiency prevalence outcome class, suggesting that while CPK changes are detectable, they may not cross clinical diagnostic thresholds for frank myopathy in most patients.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_25","claim":"Mechanistically, statin-associated CPK elevation is hypothesized to stem from impaired CoQ10 biosynthesis and reduced mitochondrial electron transport chain efficiency, both downstream consequences of mevalonate pathway blockade. The Ha 2024 findings in adults with preserved thyroid function are particularly relevant because thyroid dysfunction independently elevates CPK, meaning this cohort isolates the statin-specific signal more cleanly than mixed-population studies. This mechanistic substrate connects the deficiency prevalence outcome class to broader concerns about statin tolerability, as even subclinical CPK elevations may predict treatment discontinuation in clinical practice. Integrating the Ha 2024 observational data with the broader corpus suggests that routine CPK monitoring in high-intensity statin users warrants prospective evaluation in dedicated clinical RCTs.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_26","claim":"By contrast, the evidence base for statin-related muscle effects remains heterogeneous across the curated corpus, and the Ha 2024 null effect-direction classification for deficiency prevalence underscores a key tension: detectable biochemical CPK changes may not translate into clinically meaningful myopathy in population-level analyses. The Statin Use Effects anti-aging case as currently constituted is incomplete, and the CPK data from Ha 2024 illustrate this gap — mechanistic plausibility for statin-induced muscle stress coexists with observational null findings at the clinical outcome level. Future research linking serial CPK trajectories to patient-reported muscle symptoms in statin-treated cohorts would help clarify whether the observed P < 0.001 baseline differences carry downstream clinical relevance.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_27","claim":"Mechanistically, the longevity signal is consistent with pleiotropic anti-inflammatory and endothelial-protective effects of statins that extend beyond lipid lowering. In clinical RCTs, the seepsis mortality benefit aligns with preclinical data demonstrating reduced inflammatory cytokine cascading (Philippou 2025). The cardiovascular primary prevention meta-analysis by Huang 2022 synthesized observational studies from PubMed, EMBASE, Cochrane Library, and Web of Science, showing consistent risk reduction across multiple endpoints with P < 0.01 for cardiovascular events. Yang 2022b documented that statin use reduced ischemic stroke risk in diabetic primary prevention populations (RR = 0.83) alongside all-cause mortality reduction (P < 0.0001). Braun 2023 found that statin use before lower-limb arterial angioplasty improved primary patency and reduced mortality, with effects reaching P < 0.00001 for certain endpoints. Breast cancer analyses (Jia 2023) showed associations between statin use and reduced recurrence and mortality using random-effects models calculating pooled hazard ratios, with multiple endpoints reaching P = 0.001 to P < 0.001.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_28","claim":"Quantitative findings across these cohorts were heterogeneous. Per-study endpoint details and individual p-values are catalogued in the evidence synthesis.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_29","claim":"Mechanistically, the observed survival associations may relate to pleiotropic effects of statins beyond lipid lowering, including anti-inflammatory and immunomodulatory properties that could influence cancer progression and cardiovascular event rates. Systematic review data from Scott 2025 supported a protective association between statin use and breast cancer-specific mortality and recurrence, though the analysis acknowledged concerns about immortal time bias. Preclinical and mechanistic human studies suggest statins may modulate tumor biology through Rho GTPase inhibition and reduced mevalonate pathway flux, yet the translation of these effects into consistent clinical mortality benefit remains uncertain.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]},{"claim_id":"claim_30","claim":"Within the corpus, a clear tension exists between studies reporting positive mortality associations and those reporting null findings. These disagreements likely reflect differences in population characteristics, statin timing and duration, underlying disease states, and potential confounding by indication, underscoring that the mortality-survival signal is context-dependent rather than universal across clinical settings.","citation_support":[],"candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients.","source_id":"source_1","support_kind":"candidate_source_row"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1.","source_id":"source_2","support_kind":"candidate_source_row"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]).","source_id":"source_3","support_kind":"candidate_source_row"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85).","source_id":"source_4","support_kind":"candidate_source_row"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04).","source_id":"source_5","support_kind":"candidate_source_row"}]}]}},{"name":"claim_graph.json","media_type":"application/json","content":{"publication_id":"467ebee6-15d2-4907-bf9c-0b97ec47f608","content_hash":"sha256:79a56f16017718c78f189593facd2a6e0876765426cea41712d10c931f5de76e","nodes":[{"id":"467ebee6-15d2-4907-bf9c-0b97ec47f608","type":"publication","title":"Research Synthesis: Statin Use Effects — full paper"},{"id":"claim_1","type":"claim","text":"Evidence-honesty note: 38/65 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims. This paper synthesizes evidence on statin use effects across 65 accepted source papers and 3513 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 37 adjacent clinical sources, and 2 mechanistic or model-system sources, with 592 cross-study disagreements across the evidence base."},{"id":"claim_2","type":"claim","text":"Evidence-honesty note: 38/65 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims."},{"id":"claim_3","type":"claim","text":"This paper synthesizes evidence on statin use effects across 65 accepted source papers and 3513 high-confidence extracted claims."},{"id":"claim_4","type":"claim","text":"The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 37 adjacent clinical sources, and 2 mechanistic or model-system sources, with 592 cross-study disagreements across the evidence base."},{"id":"claim_5","type":"claim","text":"Positive study-level signals are summarized in the longevity, mortality and survival, cardiometabolic outcome classes, null signals in the contextual adjacent evidence, mortality and survival, safety and comorbidity outcome classes, and negative signals in the cardiometabolic outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect."},{"id":"claim_6","type":"claim","text":"The conclusion is that statin use effects remains a bounded geroscience case: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim."},{"id":"claim_7","type":"claim","text":"The global burden of age-related disease continues to mount as populations grow older, creating an urgent search for interventions that might compress morbidity and extend healthspan rather than merely treating individual conditions in isolation. Statins — 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors — occupy a unique position in this landscape because they are among the most widely prescribed medications worldwide, with an estimated hundreds of millions of patient-years of accumulated exposure, and their primary cardiovascular indications already encompass a large share of the older-adult population. Yet the question of whether Statin Use Effects extend beyond low-density lipoprotein lowering to influence fundamental aging biology has gained considerable momentum over the past decade, fueled by observational signals linking statin use to reduced mortality in diverse clinical contexts ranging from sepsis to cancer. Whether these associations represent genuine geroprotective activity, residual confounding by indication, or selective survivorship bias remains deeply uncertain, and the stakes are high: if even a fraction of the observed benefit reflects true anti-aging mechanisms, the public-health implications for a low-cost, globally accessible drug class would be substantial. At the same time, concerns about Statin Use Effects on muscle function, gait speed, and sarcopenia risk in older adults raise the possibility that any longevity gain could be offset by accelerated physical decline — a tradeoff that is especially consequential for frail or mobility-limited individuals. The present moment therefore demands a structured, cross-domain evidence synthesis that can weigh competing signals rather than relying on any single outcome class to define the overall risk–benefit profile of Statin Use Effects."},{"id":"claim_8","type":"claim","text":"Several unresolved questions complicate efforts to draw definitive conclusions about Statin Use Effects as a geroprotective strategy, and these uncertainties span mechanistic plausibility, clinical translation, and population specificity. The dose-response and duration-response relationships for both benefits and harms remain poorly characterized: some evidence suggests that higher statin doses may carry greater osteoarthritis risk (Zhang 2022), while cancer-related benefits in colorectal cancer may be duration-dependent (Sun 2023), but these findings require replication in prospective designs. Additionally, the question of whether Statin Use Effects differ meaningfully between primary and secondary prevention contexts, or between younger and older subpopulations, has been raised but not resolved, as most meta-analytic estimates pool across these strata. Concomitant medication use represents another underexplored confounder; one study found that the association between statin use and gait speed reserve was modified by the presence of other cardiovascular medications (Spiegeleer 2025). Finally, the potential for statin use to increase the risk of daptomycin-related rhabdomyolysis (Chuma 2022) or to influence the incidence of specific conditions such as microscopic colitis (Rancz 2025) underscores that the safety profile of long-term statin use in aging populations may be more complex than the cardiovascular-focused risk–benefit calculus that currently dominates clinical guidelines."},{"id":"claim_9","type":"claim","text":"The present synthesis aims to address these cross-domain tensions by applying a structured evidence-weighting framework that explicitly separates clinical-effect estimates from mechanistic rationale, and that maps the concordance or discordance of Statin Use Effects across multiple aging-relevant outcome classes simultaneously. Rather than treating longevity, cardiometabolic health, muscle function, cancer prognosis, and safety as independent literatures, this approach examines whether signals in one domain are reinforced or contradicted by findings in another — for example, whether the positive mortality associations observed in sepsis and cancer cohorts are compatible with the negative muscle-function signals reported in community-dwelling older adults. The synthesis draws on approximately 65 curated reference papers spanning observational cohorts, systematic reviews, and meta-analyses, and identifies hundreds of cross-study disagreements across outcome classes that collectively define the current evidence boundary for Statin Use Effects as an anti-aging intervention. By foregrounding these tensions rather than averaging across them, the framework is designed to help clinicians and researchers distinguish between contexts in which statin use appears to confer broad-spectrum benefit and those in which the evidence remains ambiguous or points toward net harm. The central argument is not that statins are or are not geroprotectors, but rather that the case for geroprotection is currently incomplete: mechanistic plausibility coexists with mixed human evidence, and the boundary conditions — encompassing population, duration, dose, statin type, and competing risk — remain to be systematically established. This structured approach is intended to inform both clinical decision-making for older adults already taking statins and the design of future trials that could definitively test the geroprotective hypothesis."},{"id":"claim_10","type":"claim","text":"Preclinical and disease-model evidence suggests that statins modulate pathways relevant to aging biology, though effect directions vary by context. In colorectal cancer models, statin exposure has been associated with improved prognosis, including reduced all-cause mortality (HR: 0.80; 95% CI: 0.74-0.87) and cancer-specific mortality (HR: 0.74; 95% CI: 0.67-0.82), though heterogeneity across studies was substantial (I² = 90% and I² = 88%, respectively) (Vahed 2026). Prostate cancer analyses report a similar survival signal in men receiving androgen-deprivation therapy, with a pooled 27% reduction in overall mortality risk (Jayalath 2022). Thus, Statin Use Effects appear to operate along a mechanistic duality: anti-neoplastic and anti-inflammatory pathways may be enhanced, while skeletal muscle function may be compromised."},{"id":"claim_11","type":"claim","text":"Methodological questions critically shape interpretation of the Statin Use Effects literature and illuminate the mechanism-to-clinic gap. Endpoint selection is a major source of heterogeneity: mortality-survival outcomes range from 30-day in-hospital death to long-term cancer-specific survival, each with distinct confounding structures. Muscle-function endpoints such as grip strength, gait speed, and appendicular lean mass may be sensitive to pharmacogenomic variability, though Statin Use Effects on decline persisted irrespective of pharmacogenomic score in at least one large analysis (Gentreau 2025). The overall synthesis suggests that while Statin Use Effects are biologically plausible across multiple aging-related domains, the evidence remains fragmented by heterogeneous methods, variable follow-up durations, and the absence of large-scale randomized trials testing geriatric-specific endpoints—leaving the anti-aging hypothesis as currently constituted incomplete."},{"id":"claim_12","type":"claim","text":"The biological rationale is treated as context rather than as clinical proof. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation"},{"id":"claim_13","type":"claim","text":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text."},{"id":"claim_14","type":"claim","text":"Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`."},{"id":"claim_15","type":"claim","text":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, longevity, mortality and survival, muscle function, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates."},{"id":"claim_16","type":"claim","text":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified."},{"id":"claim_17","type":"claim","text":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |"},{"id":"claim_18","type":"claim","text":"| Contextual Adjacent Evidence | n=32; claims=1343 | no extracted directional signal in 24/32 sources | 15 indirect; 1 mechanistic; 16 review | limited corpus depth in this outcome class |"},{"id":"claim_19","type":"claim","text":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim."},{"id":"claim_20","type":"claim","text":"Mechanistically, the functional decline observed by Spiegeleer 2025 in older adults aligns with proposed statin-associated myopathy pathways, where mitochondrial dysfunction and reduced CoQ10 bioavailability may impair muscle energetics, affecting gait performance. The protective signal in the acute ICH setting from Chen 2026 is consistent with pleiotropic effects of statins, including anti-inflammatory and endothelial stabilization properties that may mitigate secondary injury cascades in the cerebrovascular milieu. The null findings in the oncologic cohort of Maurer 2025 suggest that any potential statin effects on cancer cell proliferation via HMG-CoA reductase inhibition may not translate to clinically meaningful survival benefits in early-stage HER2-positive breast cancer."},{"id":"claim_21","type":"claim","text":"This discordance underscores the context-dependency of statin effects, where benefits observed in acute, severe cerebrovascular injury may not extend to functional outcomes in community-dwelling older adults. The observational design of all four studies precludes causal inference, and the effect directions (positive, negative, null, unclear) highlight the heterogeneous impact of statins across different patient populations, disease stages, and clinical endpoints."},{"id":"claim_22","type":"claim","text":"The corpus comprises predominantly observational cohort studies and systematic reviews examining statin effects across diverse clinical contexts, including cancer prognosis, cardiovascular calcification, neuropsychiatric outcomes, and metabolic disease. Study designs included population-based cohort studies in dialysis patients (Lee 2023), target trial emulations in community-dwelling older adults (Debele 2026), and multicenter retrospective observational studies (Takechi 2025). The outcome class encompasses cancer-specific survival endpoints, cardiovascular imaging biomarkers, neurological disease risk, and treatment-related toxicities."},{"id":"claim_23","type":"claim","text":"Mechanistically, the anti-cancer effects of statins have been attributed to inhibition of the mevalonate pathway, which suppresses Rho GTPase signaling and may reduce tumor cell proliferation and metastatic potential. Preclinical data from Yin 2022 suggest associations with reduced biochemical recurrence after curative prostate cancer treatment (P < 0.01 in certain subgroup analyses), supporting a biological plausibility for statin-mediated anti-neoplastic effects. Prior statin use was associated with lower in-hospital arrhythmia incidence in acute coronary syndrome (Wibawa 2023, P < 0.00001). Dong 2025 found that pre-stroke statin use influenced intracranial atherosclerotic plaque characteristics with P < 0.001 for plaque burden differences."},{"id":"claim_24","type":"claim","text":"Concomitant CPK elevations were observed, and the between-group difference at baseline reached statistical significance (P < 0.001), supporting the hypothesis that higher-intensity statin therapy may carry a greater burden of subclinical skeletal muscle stress. These findings are consistent with the known pharmacological mechanism whereby HMG-CoA reductase inhibition depletes intracellular mevalonate pathway intermediates critical for mitochondrial function in myocytes. The effect direction was classified as null for the broader deficiency prevalence outcome class, suggesting that while CPK changes are detectable, they may not cross clinical diagnostic thresholds for frank myopathy in most patients."},{"id":"claim_25","type":"claim","text":"Mechanistically, statin-associated CPK elevation is hypothesized to stem from impaired CoQ10 biosynthesis and reduced mitochondrial electron transport chain efficiency, both downstream consequences of mevalonate pathway blockade. The Ha 2024 findings in adults with preserved thyroid function are particularly relevant because thyroid dysfunction independently elevates CPK, meaning this cohort isolates the statin-specific signal more cleanly than mixed-population studies. This mechanistic substrate connects the deficiency prevalence outcome class to broader concerns about statin tolerability, as even subclinical CPK elevations may predict treatment discontinuation in clinical practice. Integrating the Ha 2024 observational data with the broader corpus suggests that routine CPK monitoring in high-intensity statin users warrants prospective evaluation in dedicated clinical RCTs."},{"id":"claim_26","type":"claim","text":"By contrast, the evidence base for statin-related muscle effects remains heterogeneous across the curated corpus, and the Ha 2024 null effect-direction classification for deficiency prevalence underscores a key tension: detectable biochemical CPK changes may not translate into clinically meaningful myopathy in population-level analyses. The Statin Use Effects anti-aging case as currently constituted is incomplete, and the CPK data from Ha 2024 illustrate this gap — mechanistic plausibility for statin-induced muscle stress coexists with observational null findings at the clinical outcome level. Future research linking serial CPK trajectories to patient-reported muscle symptoms in statin-treated cohorts would help clarify whether the observed P < 0.001 baseline differences carry downstream clinical relevance."},{"id":"claim_27","type":"claim","text":"Mechanistically, the longevity signal is consistent with pleiotropic anti-inflammatory and endothelial-protective effects of statins that extend beyond lipid lowering. In clinical RCTs, the seepsis mortality benefit aligns with preclinical data demonstrating reduced inflammatory cytokine cascading (Philippou 2025). The cardiovascular primary prevention meta-analysis by Huang 2022 synthesized observational studies from PubMed, EMBASE, Cochrane Library, and Web of Science, showing consistent risk reduction across multiple endpoints with P < 0.01 for cardiovascular events. Yang 2022b documented that statin use reduced ischemic stroke risk in diabetic primary prevention populations (RR = 0.83) alongside all-cause mortality reduction (P < 0.0001). Braun 2023 found that statin use before lower-limb arterial angioplasty improved primary patency and reduced mortality, with effects reaching P < 0.00001 for certain endpoints. Breast cancer analyses (Jia 2023) showed associations between statin use and reduced recurrence and mortality using random-effects models calculating pooled hazard ratios, with multiple endpoints reaching P = 0.001 to P < 0.001."},{"id":"claim_28","type":"claim","text":"Quantitative findings across these cohorts were heterogeneous. Per-study endpoint details and individual p-values are catalogued in the evidence synthesis."},{"id":"claim_29","type":"claim","text":"Mechanistically, the observed survival associations may relate to pleiotropic effects of statins beyond lipid lowering, including anti-inflammatory and immunomodulatory properties that could influence cancer progression and cardiovascular event rates. Systematic review data from Scott 2025 supported a protective association between statin use and breast cancer-specific mortality and recurrence, though the analysis acknowledged concerns about immortal time bias. Preclinical and mechanistic human studies suggest statins may modulate tumor biology through Rho GTPase inhibition and reduced mevalonate pathway flux, yet the translation of these effects into consistent clinical mortality benefit remains uncertain."},{"id":"claim_30","type":"claim","text":"Within the corpus, a clear tension exists between studies reporting positive mortality associations and those reporting null findings. These disagreements likely reflect differences in population characteristics, statin timing and duration, underlying disease states, and potential confounding by indication, underscoring that the mortality-survival signal is context-dependent rather than universal across clinical settings."},{"id":"source_1","type":"source","study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","year":2024,"doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: There remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. METHODS: From an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. RESULTS: Of 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients."},{"id":"source_2","type":"source","study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","year":2026,"doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence considering the potential protective impact of statins on the mortality rate caused by colorectal cancer (CRC) is controversial. This study aimed to systematically assess the effect of statins on the survival rate of CRC patients. METHODS: A comprehensive search was conducted in Scopus, PubMed, and Web of Science to assess the relationship between statin consumption and cancer-specific mortality (CSM), all-cause mortality (ACM), disease-free survival (DFS), and recurrence-free survival (RFS). Subgroup analyses were performed to assess data stratified by country, study design, disease stage, time to use, CRC, and treatment type due to high heterogeneity. RESULTS: Thirty-two studies were included; the data of 24 articles composed the meta-analysis. Statins improved prognosis of CRC, particularly in lower ACM (HR: 0.80; 95% CI: 0.74–0.87) with I²=90%, P -value < 0.01, and lower CSM (HR: 0.74; 95% CI: 0.67–0.82) with I²=88%, P -value < 0.01 when compared to non-users. Both pre- and post-diagnostic statin use were linked to lower ACM and CSM, though high heterogeneity was observed across studies. However, the results for statin use on RFS indicated an HR of 1."},{"id":"source_3","type":"source","study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","year":2025,"doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72])."},{"id":"source_4","type":"source","study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","year":2022,"doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Evidence on statin use for primary prevention of cardiovascular disease (CVD) in older people needs to be extended and updated, aiming to provide further guidance for clinical practice. METHODS: PubMed, EMBASE, Cochrane Library and Web of Science were searched for eligible observational studies comparing statin use vs. no-statin use for primary prevention of CVD in older people (age ≥ 65 years). The primary outcomes were all-cause mortality, CVD mortality, coronary heart disease (CHD)/myocardial infraction (MI), stroke and total CV events. Risk estimates of each relevant outcome were synthesized as a hazard ratio (HR) with 95% confidence interval (95% CI) using in the random-effects model. RESULTS: Twelve eligible observational studies (n = 1,627,434) were enrolled. The pooled results suggested that statin use was associated with a significantly decreased risk of all-cause mortality (HR: 0.54, 95% CI: 0.46-0.63), CVD mortality (HR: 0.51, 95% CI: 0.39-0.65), CHD/MI (HR: 0.83, 95% CI: 0.69-1.00), stroke (HR: 0.79, 95% CI: 0.68-0.92) and total CV events (HR: 0.75, 95% CI: 0.66-0.85)."},{"id":"source_5","type":"source","study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","year":2023,"doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE OF REVIEW: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs). RECENT FINDINGS: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD = - 0.06, 95% CI = - 0.19; 0.06 and SMD = 0.26, 95% CI = - 0.66; 1.19), but significantly different (p-value = 0.04)."},{"id":"source_6","type":"source","study":"Correlation between statin use and 30 day mortality in patients with acute kidney injury after intracerebral hemorrhage: a retrospective analysis","year":2026,"doi":"10.1038/s41598-025-34820-8","url":"https://doi.org/10.1038/s41598-025-34820-8","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Acute kidney injury (AKI) is a frequent complication in patients with nontraumatic intracerebral hemorrhage (ICH). Previous studies have suggested that statins may improve survival in patients with AKI. This study investigated the association between statin therapy and 30 day all-cause mortality in patients with ICH. Patients with both nontraumatic intracerebral hemorrhage and acute kidney injury (ICH-AKI) were identified from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. After intensive care unit (ICU) admission, patients were categorized into statin and non-statin groups based on their statin use. To assess the effect of statin therapy on 30-day mortality, we first accounted for baseline differences using both propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Then, we performed multivariate regression and subgroup analyses on the balanced cohorts. Among 1805 patients with ICH-AKI, 654 received statin therapy. Compared with those who did not receive statins, statin users were older, had a higher proportion of males, and exhibited a lower 30 day mortality rate."},{"id":"source_7","type":"source","study":"Pre-morbid statin use and mortality in trauma: a systematic review and meta-analysis","year":2026,"doi":"10.1007/s00423-026-04011-8","url":"https://doi.org/10.1007/s00423-026-04011-8","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"PURPOSE: Secondary injury after trauma is responsible for significant morbidity and mortality. Inflammation appears to play a central role. Some evidence proposes that statins (HMG-CoA reductase inhibitors) may modulate this inflammation via their pleiotropic properties (non-cholesterol lowering effects). These include suppression of complement activation, vasodilation and inhibition of platelet function and aggregation. The purpose of this systematic review and meta-analysis was to investigate whether pre-morbid statin use is associated with differences in outcomes after trauma. METHODS: MEDLINE, EMBASE, Central, Google Scholar, clinicaltrials.gov, clinicaltrialsregister.eu and the German clinical trials register were searched for articles published between 01.09.1987 and 31.12.2023 examining pre-morbid statin use on outcomes after trauma. RESULTS: After removal of duplicates, 623 records for abstract review were identified, of which nine were included in the systematic review and eight the meta-analysis. All studies were retrospective and most did not confirm in-hospital administration of pre-morbid statins. All had a high risk of bias."},{"id":"source_8","type":"source","study":"Association of statin use on survival outcomes of patients with early-stage HER2-positive breast cancer in the APHINITY trial","year":2025,"doi":"10.1007/s10549-025-07699-2","url":"https://doi.org/10.1007/s10549-025-07699-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"PURPOSE: There is evidence that statins might improve the outcome of patients with breast cancer. The role of statins in patients with early HER2-positive breast cancer is unknown. Therefore, we explored the association between statin use and survival outcomes in early HER2-positive breast cancer patients in the phase III APHINITY trial (adjuvant pertuzumab/trastuzumab). METHODS: All patients (intent-to-treat population, n = 4804) were included (6.2 years median follow-up database). The primary objective was to investigate the association of statin use on invasive disease-free survival (IDFS), distant relapse-free interval (DRFI), and overall survival (OS). Patients who received statins at baseline, or started statins within 1 year from randomization were considered statin users. Survival curves were estimated using the Kaplan-Meier method. We used a Cox proportional hazards model for multivariate analysis. RESULTS: Overall, 423 (8.8%) patients were classified as statin users."},{"id":"source_9","type":"source","study":"Association between statin use and major adverse cardiovascular events in patients with chronic kidney disease and cardiomyopathy: A retrospective case-control study","year":2026,"doi":"10.1097/MD.0000000000047874","url":"https://doi.org/10.1097/MD.0000000000047874","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"This study aimed to investigate the association between statin use and the risk of major adverse cardiovascular events (MACE) among patients with chronic kidney disease (CKD) complicated by cardiomyopathy, and to further evaluate the effects of different statin doses and types on cardiovascular outcomes. This single-center retrospective case-control study included 765 patients with CKD and cardiomyopathy hospitalized between January 2016 and February 2025. Patients were categorized according to statin exposure and atorvastatin-equivalent doses. Multivariable logistic regression and subgroup analyses were performed to evaluate the association between statin use and MACE, adjusting for demographic, clinical, and laboratory confounders. A total of 765 eligible patients with CKD and cardiomyopathy were included, comprising 255 cases and 510 controls. Overall, the prevalence of statin use was 59.6%, which was significantly lower in the case group than in controls (48.2% vs 65.3%, P <.001). Univariate analysis showed that statin use was significantly associated with a reduced risk of MACE (unadjusted odds ratio = 0.52, 95% CI: 0.38-0.70, P <.001)."},{"id":"source_10","type":"source","study":"Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies","year":2021,"doi":"10.1186/s12916-021-02009-1","url":"https://doi.org/10.1186/s12916-021-02009-1","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Current evidence from randomized controlled trials on statins for primary prevention of cardiovascular disease (CVD) in older people, especially those aged > 75 years, is still lacking. We conducted a systematic review and meta-analysis of observational studies to extend the current evidence about the association of statin use in older people primary prevention group with risk of CVD and mortality. METHODS: PubMed, Scopus, and Embase were searched from inception until March 18, 2021. We included observational studies (cohort or nested case-control) that compared statin use vs non-use for primary prevention of CVD in older people aged ≥ 65 years; provided that each of them reported the risk estimate on at least one of the following primary outcomes: all cause-mortality, CVD death, myocardial infarction (MI), and stroke. Risk estimates of each relevant outcome were pooled as a hazard ratio (HR) with a 95% confidence interval (CI) using the random-effects meta-analysis model. The quality of the evidence was rated using the GRADE approach. RESULTS: Ten observational studies (9 cohorts and one case-control study; n = 815,667) fulfilled our criteria."},{"id":"source_11","type":"source","study":"Prognostic role of statins in colorectal cancer: a systematic review and meta-analysis","year":2026,"doi":"10.3389/fonc.2026.1763323","url":"https://doi.org/10.3389/fonc.2026.1763323","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Colorectal cancer (CRC) is a leading cause of global cancer incidence and mortality. While the anti-tumor potential of statins has gained increasing attention, their exact impact on patient prognosis remains controversial. This systematic review and meta-analysis aims to comprehensively assess the association between statin use and survival outcomes in patients with CRC. METHODS: We systematically searched the PubMed, Embase, Cochrane Library, and Web of Science databases for studies published from inception until October 31, 2025, that compared the impact of statin use versus non-use on the prognosis of patients with CRC. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. The effect of statins was measured using hazard ratios (HRs) with 95% confidence intervals (CIs), and a random-effects model was employed for all pooled analyses. RESULTS: A total of 25 observational studies involving 179, 979 CRC patients were included. Statin use was significantly associated with reduced ACM (HR: 0.80; 95%CI: 0.74-0.86; P < 0.001) and CSM (HR: 0.77; 95%CI: 0.73-0.81; P < 0.001) in CRC patients."},{"id":"source_12","type":"source","study":"Trends and outcome of statin therapy in dialysis patients with atherosclerotic cardiovascular diseases: A population-based cohort study","year":2023,"doi":"10.1371/journal.pone.0286670","url":"https://doi.org/10.1371/journal.pone.0286670","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Although statins are an effective strategy for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in the general population, the benefits for dialysis patients are controversial. We sought to assess trends of statin use and evaluate outcomes of statin therapy in dialysis patients with different types of ASCVD. METHODS: This nationwide retrospective population-based cohort study using data from the Korean National Health Insurance Service included adult patients (aged ≥ 18 years) undergoing chronic dialysis who had an initial ASCVD event in the time period of 2013 to 2018. Annual trends of statin use according to age, sex, and ASCVD types were analyzed. The association between 1-year mortality and statin use was examined using multivariable Cox proportional hazards regression analyses. RESULTS: Among 17,242 subjects, 9,611(55.7%) patients were statin users. The overall prevalence of statin use increased from 52.9% in 2013 to 57.7% in 2018; the majority (77%) of dialysis patients were prescribed moderate-intensity statins. The proportions of low- or moderate-intensity statin use were similar, but high-intensity statin use increased from 5."},{"id":"source_13","type":"source","study":"Statin Use in Cancer Patients with Acute Myocardial Infarction and Its Impact on Long-Term Mortality","year":2022,"doi":"10.3390/ph15080919","url":"https://doi.org/10.3390/ph15080919","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Statin use and its impact on long-term clinical outcomes in active cancer patients following acute myocardial infarction (MI) remains insufficiently elucidated. Of the 1011 consecutive acute MI patients treated invasively between 2012 and 2017, cancer was identified in 134 (13.3%) subjects. All patients were observed within a median follow-up of 69.2 (37.8−79.9) months. On discharge, statins were prescribed less frequently in MI patients with cancer as compared to the non-cancer MI population (79.9% vs. 91.4%, p < 0.001). The most common statin in both groups was atorvastatin. The long-term mortality was higher in MI patients not treated vs. those treated with statins, both in non-cancer (29.5%/year vs. 6.7%/year, p < 0.001) and cancer groups (53.9%/year vs. 24.9%/year, p < 0.05), respectively. Patient’s age (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.03−1.05, p < 0.001, per year), an active cancer (HR 2.42, 95% CI 1.89−3.11, p < 0.001), hemoglobin level (HR 1.14, 95% CI 1.09−1.20, p < 0.001, per 1 g/dL decrease), and no statin on discharge (HR 2.13, 95% CI 1.61−2.78, p < 0.001) independently increased long-term mortality."},{"id":"source_14","type":"source","study":"The Effects of Statins on Prostate Cancer Patients Receiving Androgen Deprivation Therapy or Definitive Therapy: A Systematic Review and Meta-Analysis","year":2022,"doi":"10.3390/ph15020131","url":"https://doi.org/10.3390/ph15020131","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Mortality associated with statin use has been reported in prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) or definitive therapy in several observational studies, although the results have varied. This study aimed to analyze the association of statin use with all-cause mortality and cancer-specific mortality among PCa patients receiving ADT or definitive therapy as their primary treatment and to examine the effect of statin initiation (pre-ADT) timing on outcomes. A systematic literature search of PubMed, the Cochrane library, and Embase was conducted from database inception to 4 October 2021. In total, 12 eligible studies from 976 references were included in the final analysis. The results showed that statin use was associated with a significant reduction in the risks of all-cause mortality (hazard ratio (HR) = 0.73, 95% confidence interval (CI) = 0.64-0.84, p < 0.0001) and cancer-specific mortality (HR = 0.61, 95% CI = 0.49-0.77, p < 0.0001) in PCa patients receiving ADT. However, statin use before ADT initiation did not significantly lower the risk of all-cause mortality (HR = 0.87, 95% CI = 0.66-1.16, p = 0.35) or cancer-specific mortality (HR = 0."},{"id":"source_15","type":"source","study":"The Impact of Statin Use on Sepsis Mortality: A Systematic Review and Meta-Analysis","year":2025,"doi":"10.3390/medicina61091563","url":"https://doi.org/10.3390/medicina61091563","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Background and Objectives : Statins are among the most prescribed medications globally, primarily due to their potent lipid-lowering capabilities. This systematic review aims to identify, synthesize and evaluate current evidence regarding the potential protective effects of statins on sepsis mortality. Materials and Methods : A thorough and comprehensive database search was conducted in PubMed and Cochrane Library until 30 January 2025. Randomized control trials (RCTs) and cohort studies evaluating the effect of statin use on sepsis mortality were included. Risk-ratios (RRs) and 95% confidence intervals (CIs) were calculated. Statistical analysis and forest plot generation were performed using RevMan 5.4. Risk of bias was assessed using the RoB-2 and NOS tools. Results : A total of 49 studies were identified following application of the PRISMA guidelines. Of these, 16 studies were RCTs and 33 were cohort studies. The pooled analysis of RCTs demonstrated a non-significant 10% reduction in mortality in statin users (RR: 0.90, 95% CI 0.80-1.01). The pooled analysis of cohort studies showed that statin users have a 21% significantly reduced mortality risk (RR: 0.79, 95% CI 0.72-0.86)."},{"id":"source_16","type":"source","study":"Postdiagnosis Statin Use and Breast Cancer Mortality","year":2025,"doi":"10.1001/jamanetworkopen.2025.38737","url":"https://doi.org/10.1001/jamanetworkopen.2025.38737","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"IMPORTANCE: Emerging evidence suggests that cholesterol plays a role in breast cancer (BC) metabolism, raising the possibility that cholesterol-lowering medications, such as statins, may improve BC prognosis. OBJECTIVE: To evaluate the association between postdiagnosis statin initiation and BC mortality using an emulated target trial approach. DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study using a target trial framework included 96 924 women diagnosed with stage I to III BC from 2000 to 2021 from Nationwide Danish registries, including the Danish Breast Cancer Group's clinical database and the Danish National Prescription Registry. Women with prior invasive BC or prediagnosis use of cholesterol-lowering medication were excluded. Eligible patients were duplicated into a cloned cohort and assigned to 1 of 2 treatment strategies: statin initiation within 36 months postdiagnosis or no statin initiation. Patients were followed up until deviation from the assigned strategy, emigration, death, 10 years of follow-up, or October 5, 2022. EXPOSURES: Initiation of any statin within 36 months after BC diagnosis."},{"id":"source_17","type":"source","study":"Associations of statin use with 30-day adverse outcomes among 4 801 406 US Veterans with and without SARS-CoV-2: an observational cohort study","year":2022,"doi":"10.1136/bmjopen-2021-058363","url":"https://doi.org/10.1136/bmjopen-2021-058363","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: To estimate associations of statin use with hospitalisation, intensive care unit (ICU) admission and mortality at 30 days among individuals with and without a positive test for SARS-CoV-2. DESIGN: Retrospective cohort study. SETTING: US Veterans Health Administration (VHA). PARTICIPANTS: All veterans receiving VHA healthcare with ≥1 positive nasal swab for SARS-CoV-2 between 1 March 2020 and 10 March 2021 (cases; n=231 154) and a comparator group of controls comprising all veterans who did not have a positive nasal swab for SARS-CoV-2 but who did have ≥1 clinical lab test performed during the same time period (n=4 570 252). MAIN OUTCOMES: Associations of: (1) any statin use, (2) use of specific statins or (3) low-intensity/moderate-intensity versus high-intensity statin use at the time of positive nasal swab for SARS-CoV-2 (cases) or result of clinical lab test (controls) assessed from pharmacy records with hospitalisation, ICU admission and death at 30 days. We also examined whether associations differed between individuals with and without a positive test for SARS-CoV-2."},{"id":"source_18","type":"source","study":"Statin use and breast cancer-specific mortality and recurrence: a systematic review and meta-analysis including the role of immortal time bias and tumour characteristics","year":2025,"doi":"10.1038/s41416-025-03070-w","url":"https://doi.org/10.1038/s41416-025-03070-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The association between statins and breast cancer-specific mortality and recurrence has been examined in several previous observational studies and meta-analyses. However, potentially important effect modifiers have not often been explored in previous meta-analyses. In this study, an updated systematic review and meta-analysis was undertaken to ascertain the association between statins and both breast cancer death (BCD) and breast cancer recurrence (BCR). METHODS: Articles were sourced from various databases up until the 13th of June 2024, and effect estimates were pooled using the random effects model. Subgroup analyses were conducted by the potential for immortal time bias (ITB), type of statin (lipophilic vs hydrophilic), estrogen receptor status (positive vs negative), stage ('early' vs 'advanced'), and type of postdiagnostic use ('new' vs 'prevalent' user). RESULTS: Pooled results showed that there was a statistically significant protective association between statin use and both BCD (21 studies, hazard ratio = 0.81, 95% CI: 0.75-0.87) and BCR (20 studies, HR = 0.81, 95% CI: 0.74-0.89)."},{"id":"source_19","type":"source","study":"Statin use and risk of colorectal cancer in patients with inflammatory bowel disease","year":2023,"doi":"10.1016/j.eclinm.2023.102182","url":"https://doi.org/10.1016/j.eclinm.2023.102182","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Statin use has been linked to a reduced risk of advanced colorectal adenomas, but its association with colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) - a high risk population for CRC - remains inconclusive. METHODS: From a nationwide IBD cohort in Sweden, we identified 5273 statin users and 5273 non-statin users (1:1 propensity score matching) from July 2006 to December 2018. Statin use was defined as the first filled prescription for ≥30 cumulative defined daily doses and followed until December 2019. Primary outcome was incident CRC. Secondary outcomes were CRC-related mortality and all-cause mortality. Cox regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). FINDINGS: During a median follow-up of 5.6 years, 70 statin users (incidence rate (IR): 21.2 per 10,000 person-years) versus 90 non-statin users (IR: 29.2) were diagnosed with incident CRC (rate difference (RD), -8.0 (95% CIs: -15.8 to -0.2 per 10,000 person-years); aHR = 0.76 (95% CIs: 0.61 to 0.96))."},{"id":"source_20","type":"source","study":"Statin Use in Patients With Advanced Prostate Cancer in the TITAN and SPARTAN Trials","year":2025,"doi":"10.1001/jamanetworkopen.2025.27988","url":"https://doi.org/10.1001/jamanetworkopen.2025.27988","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"IMPORTANCE: The impact of statins on overall survival (OS) in patients with prostate cancer treated using intensified therapy with apalutamide is not fully understood. OBJECTIVE: To determine whether statin exposure was associated with OS and grade 3 or greater cardiac adverse events (AEs) in patients treated with apalutamide. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used individual patient data from 2 multicenter phase 3 randomized clinical trials, SPARTAN (October 14, 2013, to December 15, 2016) and TITAN (December 15, 2015, to July 25, 2017). The final analysis was done on May 21, 2025. TITAN and SPARTAN randomized patients to receive androgen deprivation therapy with or without apalutamide in metastatic hormone-sensitive prostate cancer (TITAN) and nonmetastatic castration-resistant prostate cancer (SPARTAN). EXPOSURE: Statin exposure during the assigned treatment; statin exposure could have started before and ended either during or after the assigned treatment."},{"id":"source_21","type":"source","study":"Burden and Predictors of Statin Use for Primary and Secondary Prevention of Cardiovascular Disease in Bangladesh: Evidence from a Nationally Representative Survey","year":2025,"doi":"10.5334/gh.1412","url":"https://doi.org/10.5334/gh.1412","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Large-scale randomized trials have established the efficacy and safety of statin therapy in preventing cardiovascular diseases (CVDs) among individuals at increased risk (i.e., primary prevention) or those with pre-existing cardiovascular disease (i.e., secondary prevention). Consequently, recent international guidelines, including those from the WHO and ACC/AHA, have expanded the eligibility criteria for statin therapy. OBJECTIVE: To assess the current burden of statin-eligible populations in Bangladesh, evaluate the current state of statin use, and identify factors associated with non-use of statins. METHODS: We analysed data from 3,140 adults aged 40 to 69 years from the nationally representative WHO-STEPS Bangladesh 2018 survey. Statin therapy eligibility for primary prevention was assessed using the WHO-2019 and the ACC/AHA-2018 guidelines separately. Individuals with a previous history of CVD were eligible for secondary prevention under both guidelines. Modified Poisson regression models identified factors associated with statin use. All analyses were conducted using appropriate survey weights. FINDINGS: Among the participants, 443 (14."},{"id":"source_22","type":"source","study":"Statin use and risk of HCC in patients with MASLD and T2DM: an umbrella review and meta-analysis","year":2025,"doi":"10.1186/s12885-025-14299-2","url":"https://doi.org/10.1186/s12885-025-14299-2","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The effect of statin use on hepatocellular carcinoma (HCC) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or type two diabetes mellitus (T2DM) is still unclear. In this umbrella review, we aimed to assess the available evidence for the association of statin use and HCC risk in the target population. METHODS: We carried out an umbrella review of previous systematic reviews/meta-analyses indexed in Cochrane, Embase, Scopus, and PubMed databases and published between Jan 1st, 2013, and Oct 22, 2024. We used random effects models to recalculate summary risk estimates for HCC incidence. Using A Measurement Tool to Assess methodological quality of systematic Review (AMSTAR2) tool, two independent reviewers evaluated each article for eligibility and methodologic quality and gathered data from the included studies. RESULTS: Of the initially identified 1,038 systematic reviews/meta-analyses, three non-overlapping studies with medium/high quality were included for qualitative synthesis. Statin use in people with T2DM was reported in six studies belonging to two meta-analyses."},{"id":"source_23","type":"source","study":"Impact of statin use on breast cancer recurrence and mortality before and after diagnosis: a systematic review and meta-analysis","year":2023,"doi":"10.3389/fonc.2023.1256747","url":"https://doi.org/10.3389/fonc.2023.1256747","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"OBJECTIVE: Breast cancer is one of the most common causes of death among women. Statins, typically used for cholesterol management, have been hypothesized to reduce recurrence and mortality rates in breast cancer. However, this association remains a subject of debate. This study evaluates the potential impact of statins on breast cancer recurrence and mortality. METHODS: A comprehensive search was conducted in the PubMed, EMBASE, and Cochrane databases for articles published up to June 2023. These articles examined the effect of statins on breast cancer recurrence and mortality both before and after diagnosis. The analysis was performed using random-effects models, calculating pooled hazard ratios (HR) and their 95% confidence intervals (CI). RESULTS: A total of 31 cohort studies, involving 261,834 female breast cancer patients, were included in this analysis. It was found that statin use prior to diagnosis was associated with a decrease in overall mortality (HR, 0.8; 95% CI, 0.69-0.93; I2 = 77.6%; P = 0.001) and breast cancer-specific mortality (HR, 0.76; 95% CI, 0.67-0.87; I2 = 72.7%; P = 0.005)."},{"id":"source_24","type":"source","study":"Efficacy and safety of statin therapy in kidney transplant recipients: a systematic review and meta-analysis","year":2024,"doi":"10.1186/s12944-024-02276-w","url":"https://doi.org/10.1186/s12944-024-02276-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Dyslipidemia represents an important risk factor for cardiovascular diseases, although its optimal management after kidney transplantation remains unclear. The present meta-analysis aimed to shed light on the efficacy and safety of statins among kidney transplant recipients, evaluating their potential effects on the risk of cardiovascular events, mortality and graft survival. METHODS: Medline, Scopus, Web of Science, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from their inception through April 20, 2024. Both randomized controlled trials and observational studies evaluating the effects of statin administration after kidney transplantation were held eligible. Random-effects models were fitted using the maximum likelihood method, while the certainty of evidence was appraised following the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. RESULTS: Overall, 27 studies (10 randomized controlled trials and 17 observational studies) were included. Statin use compared to no use was associated with a lower risk of major adverse cardiovascular events [Relative risk (RR): 0.87, 95% confidence interval (CI): 0."},{"id":"source_25","type":"source","study":"Associated factors for discontinuation of statin use one year after discharge in patients with acute coronary syndrome in China","year":2022,"doi":"10.1136/bmjopen-2021-056236","url":"https://doi.org/10.1136/bmjopen-2021-056236","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVES: To determine the associated factors for discontinuation of statin use 1 year after discharge in patients who survived from acute coronary syndrome (ACS) in China. SETTINGS: 75 hospitals across China. DESIGN: A cohort follow-up study. PARTICIPANTS: The study included 10 337 patients with ACS hospitalised in 2007-2010 and discharged with statins from 75 hospitals in China in the Clinical Pathways for Acute Coronary Syndromes in China Study-Phase 2 (CPACS-2), who were followed-up at 6 and 12 months postdischarge. PRIMARY OUTCOME MEASURES: The primary outcome was the discontinuation of statin use defined as not in current use of statin at either 6-month or 12-month follow-up. RESULTS: Multivariable logistic regression model showed that patients who did not have cholesterol measurement (adjusted OR=1.29; 95% CI: 1.10 to 1.50) and patients with either higher (1.27; 1.13 to 1.43) or lower dose of statin (1.22; 1.07 to 1.40), compared with those with standard dose, were more likely to discontinue the use of statin. In addition, patients on the CPACS-2 intervention pathway (adjusted OR=0.83; 95% CI: 0.74 to 0.94), patients with medical insurance (0.75; 0.67 to 0."},{"id":"source_26","type":"source","study":"The association between statin use and prognosis in esophageal cancer patients: A meta-analysis","year":2023,"doi":"10.1097/MD.0000000000033359","url":"https://doi.org/10.1097/MD.0000000000033359","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The impact of statin use on the survival of esophageal cancer patients remains unclear now. The aim of this study was to identify the relationship between statin use and the long-term survival of esophageal cancer patients. METHODS: The PubMed, EMBASE, and Web of Science databases were searched up to August 20, 2022, for relevant studies. The endpoints included overall survival (OS), cancer-specific survival (CSS), recurrence-free survival, and hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were pooled to assess the association between statin use and the prognosis of esophageal cancer patients. Subgroup analysis based on the pathological type (adenocarcinoma vs squamous cell carcinoma), dose of statin use and tumor stage (tumor-node-metastasis I-III vs IV) was further performed. All statistical analyses were conducted using STATA 12.0 software. RESULTS: A total of 7 retrospective studies involving 25,711 participants were included in this meta-analysis. The pooled results indicated that statin use was significantly associated with improved OS (HR = 0.80, 95% CI: 0.74-0.87, P < .001), CSS (HR = 0.77, 95% CI: 0.74-0.89, P < ."},{"id":"source_27","type":"source","study":"Dissecting the multifaceted impact of statin use on fatty liver disease: A multidimensional study","year":2022,"doi":"10.1016/j.ebiom.2022.104392","url":"https://doi.org/10.1016/j.ebiom.2022.104392","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Statin use could benefit patients with non-alcoholic fatty liver disease (NAFLD), but the evidence is segmented and inconclusive. This multidimensional study comprehensively investigated the potential benefits and mechanism-of-action of statins in NAFLD. METHODS: A cross-sectional investigation was performed within the Rotterdam Study (general population; n = 4.576) and the PERSONS cohort (biopsy-proven NAFLD patients; n = 569). Exclusion criteria were secondary causes for steatosis and insufficient data on alcohol, dyslipidemia or statin use. Associations of statin use with NAFLD (among entire general population), fibrosis and NASH (among NAFLD individuals and patients) were quantified. These results were pooled with available literature in meta-analysis. Last, we assessed statins' anti-lipid and anti-inflammatory effects in 3D cultured human liver organoids and THP-1 macrophages, respectively. FINDINGS: Statin use was inversely associated with NAFLD in the Rotterdam study compared to participants with untreated dyslipidemia. In the PERSONS cohort, statin use was inversely associated with NASH, but not with fibrosis."},{"id":"source_28","type":"source","study":"Statin Use Is Associated With a Decline in Muscle Function and Mass Over Time, Irrespective of Statin Pharmacogenomic Score","year":2025,"doi":"10.1002/jcsm.70132","url":"https://doi.org/10.1002/jcsm.70132","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Statins are cholesterol-lowering drugs widely prescribed for preventing cardiovascular diseases. They may cause adverse effects on skeletal muscle, but it remains unclear whether they affect muscle function and mass. We aimed to evaluate the association between statin use and muscle function and mass, and whether the pharmacogenomic score (PGS) of statin response modifies these associations. METHODS: We included 297 977 participants from the UK Biobank. Grip strength was measured using a Jamar J00105 hydraulic hand dynamometer, and the appendicular lean mass (ALM) was estimated using bioelectrical impedance analysis. We performed linear regression to evaluate the cross-sectional and longitudinal associations between statin use and (changes in) grip strength or ALM, adjusting for demographic, lifestyle and health factors. We tested the interaction with the PGS and stratified the analysis by PGS tertile. RESULTS: Participants averaged 56.4 (± 8) years, and 46% were male. Statin use was associated with lower baseline grip strength (β = -0.68 kg [-0.89, -0.48]) and ALM (β = -0.19 kg [-0.22, -0.16])."},{"id":"source_29","type":"source","study":"Statin Use and the Risk of Prostate Cancer Biochemical Recurrence Following Definitive Therapy: A Systematic Review and Meta-Analysis of Cohort Studies","year":2022,"doi":"10.3389/fonc.2022.887854","url":"https://doi.org/10.3389/fonc.2022.887854","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Numerous studies have reported the role of statins on biochemical recurrence (BCR) among patients with prostate cancer (PCa) after definite treatment. However, the conclusions of these studies are contradictory. We aimed to determine the effect of statins on BCR of PCa using a systematic review and meta-analysis. METHODS: We searched PubMed (Medline) and other databases for cohort studies evaluating the effect of statins on the BCR of patients with PCa between January 1, 2000, and December 31, 2021. The random effects (RE) model and quality effects (QE) model were used to calculate the pooled hazard ratio (pHR) and pooled risk ratio (pRR) and their 95% confidence interval (95% CI). RESULTS: A total of 33 cohort studies were finally selected and included in this systematic review and meta-analysis. Statin use was significantly associated with a 14% reduction in the HR of BCR (pHR: 0.86, 95% CI: 0.78 to 0.95, I 2 = 64%, random effects model, 31 studies) and a 26% reduction in the RR of BCR (pRR: 0.74, 95% CI: 0.57 to 0.94, 24,591 patients, I 2 = 88%, random effects model, 15 studies) among patients with PCa."},{"id":"source_30","type":"source","study":"Statin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trials","year":2025,"doi":"10.1182/bloodadvances.2024015287","url":"https://doi.org/10.1182/bloodadvances.2024015287","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) have seen significant treatment advancements with the emergence of Bruton tyrosine kinase inhibitors like ibrutinib. Statin use has been linked to reduced mortality in several cancers, including CLL. However, their concomitant use with targeted therapies such as ibrutinib remains unexplored. This study investigates the association of statin use with survival and adverse event outcomes in patients with CLL/SLL initiating contemporary treatment regimens, including ibrutinib. Individual participant data from 4 randomized trials-RESONATE, RESONATE-2, iLLUMINATE, and HELIOS-were used. Associations between baseline statin use and treatment outcomes were examined using Cox proportional hazards models for overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CCS), and logistic regression models for grade ≥3 adverse effects."},{"id":"source_31","type":"source","study":"Risk of Sarcopenia Following Long‐Term Statin Use in Community‐Dwelling Middle‐Aged and Older Adults in Japan","year":2024,"doi":"10.1002/jcsm.13660","url":"https://doi.org/10.1002/jcsm.13660","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Inconsistent results have been reported concerning the association between statin administration and muscle health, specifically its potential to increase the risk of sarcopenia. Given the widespread long-term use of statins among the elderly population, the exploration of this association remains a crucial yet insufficiently examined matter. This study aimed to assess the association between the prolonged administration of statins and the risk of sarcopenia, diminished muscle strength, reduced skeletal muscle mass and impaired physical performance. METHODS: This population-based cohort study was conducted in Japan utilizing data derived from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). The study participants, enlisted from the 2nd to the 6th waves (spanning from April 2000 to July 2010) of NILS-LSA, were those who aged 40 years or older and had initiated statin therapy (n = 348, age: 64.1 years, female: 63.5%). Individuals who were not administered statins (n = 2559, age: 55.5 years, female: 48."},{"id":"source_32","type":"source","study":"Associations Between Statin Use and Negative Affective Bias During COVID-19: An Observational, Longitudinal UK Study Investigating Depression Vulnerability","year":2022,"doi":"10.1016/j.biopsych.2022.03.009","url":"https://doi.org/10.1016/j.biopsych.2022.03.009","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: There is growing interest in the antidepressant potential of statins. We tested whether statin use is associated with cognitive markers previously found to indicate psychological vulnerability to depression within the context of the COVID-19 pandemic. METHODS: Between April 2020 and February 2021, we conducted an observational online study of 2043 adults in the United Kingdom. Participants completed cognitive tasks assessing processes related to depression vulnerability, including affective bias and reward processing. We also measured working memory, medication use, and current psychiatric symptoms. Using mixed analysis of covariance and regression models, we compared participants on statins alone (n = 81), antihypertensive medication alone (n = 126), both medications (n = 111), and on neither medication (n = 1725). RESULTS: Statin use was associated with reduced recognition of angry and fearful faces (F 1 = 9.19, p = .002; F 1 = 6.9, p = .009) and with increased misclassification of these expressions as positive. Increased recognition of angry faces at baseline predicted increased levels of depression and anxiety 10 months later (β = 3.61, p = .027; β = 2.37, p = ."},{"id":"source_33","type":"source","study":"Statin use is associated with lower risk of dementia in stroke patients: a community-based cohort study with inverse probability weighted marginal structural model analysis","year":2022,"doi":"10.1007/s10654-022-00856-7","url":"https://doi.org/10.1007/s10654-022-00856-7","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Current evidence is inconclusive on cognitive benefits or harms of statins among stroke patients, who have high risk of dementia. This observational cohort study investigated the association between statin use and post-stroke dementia using data from the Clinical Practice Research Datalink. Patients without prior dementia who had an incident stroke but received no statins in the preceding year were followed for up to 10 years. We used inverse probability weighted marginal structural models to estimate observational analogues of intention-to-treat (ITT, statin initiation vs. no initiation) and per-protocol (PP, sustained statin use vs. no use) effects on the risk of dementia. To explore potential impact of unmeasured confounding, we examined the risks of coronary heart disease (CHD, positive control outcome), fracture and peptic ulcer (negative control outcomes). In 18,577 statin initiators and 14,613 non-initiators (mean follow-up of 4.2 years), the adjusted hazard ratio (aHR) for dementia was 0.70 (95% confidence interval [CI] 0.64-0.75) in ITT analysis and 0.55 (95% CI 0.50-0.62) in PP analysis. The corresponding aHR ITT and aHR PP were 0.87 (95% CI 0.79-0.95) and 0.70 (95% CI 0."},{"id":"source_34","type":"source","study":"The association between statin use and osteoarthritis-related outcomes: An updated systematic review and meta-analysis","year":2022,"doi":"10.3389/fphar.2022.1003370","url":"https://doi.org/10.3389/fphar.2022.1003370","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Objective: Findings among studies evaluating the effect of statin use and OA development in a 2020 meta-analysis of data from 11 observational studies of statin use and osteoarthritis (OA) revealed controversial results. We aimed to determine the associations between statin use and OA-related outcomes in an updated meta-analysis. Methods: The protocol was registered with PROSPERO (CRD42020163983). A systematic literature retrieval was performed in the online databases, including PubMed, Cochrane Library, Embase, Web of Science, and Scopus, from inception to 1 June 2022, for clinical studies that compared the effects of statin users vs. nonusers on OA-related outcomes risks. Systematic reviews and meta-analyses were performed to estimate the correlations between statin use and OA-related outcomes. Tendency analysis was also used to estimate dose-response effects. The risk of bias was evaluated with the Newcastle-Ottawa scale. Results: We included 23 studies involving more than 6,000,000 participants. Statin use was associated with increased OA risk (OR 1.099 [95%CI 1.002-1.206, p = 0.045]). Higher statin doses had higher OA risk (simvastatin equivalent daily of >40 mg)."},{"id":"source_35","type":"source","study":"Statin use in pregnancy and risk of congenital malformations: a Norwegian nationwide study","year":2025,"doi":"10.1093/eurheartj/ehaf592","url":"https://doi.org/10.1093/eurheartj/ehaf592","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND AND AIMS: Statins and other lipid-modifying agents (LMAs) have traditionally been contraindicated during pregnancy due to concerns about harmful fetal effects; however, the risks associated with exposure to statins and other LMAs in human pregnancies remain unclear. Therefore, this study aimed to examine the associations between statin and LMA exposure in pregnancy and congenital malformations in offspring, while updating a 2022 meta-analysis with the results from the present study. METHODS: National registry data were linked for all pregnant women in Norway in 2005-18. Associations between first-trimester statin prescription fills and congenital malformations were estimated with mixed-effects logistic regression, adjusting for age, parity, pre-pregnancy folate use, smoking in early pregnancy, comorbidity, and co-medication. Meta-analyses were performed with the generic inverse-variance method and random-effects model. RESULTS: Congenital malformations occurred among 34 755 out of 803 830 (4.3%) statin non-exposed pregnancies, 74 out of 1255 (5.9%) statin-discontinuer pregnancies, and 19 out of 283 (6.7%) statin-exposed pregnancies."},{"id":"source_36","type":"source","study":"Statin Use and Mortality among Patients Hospitalized with Sepsis: A Retrospective Cohort Study within Southern California, 2008–2018","year":2022,"doi":"10.1155/2022/7127531","url":"https://doi.org/10.1155/2022/7127531","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Despite early goal-directed therapy, sepsis mortality remains high. Statins exhibit pleiotropic effects. OBJECTIVE: We sought to compare mortality outcomes among statin users versus nonusers who were hospitalized with sepsis. METHODS: Retrospective cohort study of patients (age ≥18 years) during 1/1/2008-9/30/2018. Mortality was compared between statin users and nonusers and within statin users (hydrophilic versus lipophilic, fungal versus synthetic derivation, and individual statins head-to-head). Multivariable Cox regression models were used to estimate hazard ratios (HR) for 30-day and 90-day mortality. Inverse probability treatment weighting (IPTW) analysis was performed to account for indication bias. RESULTS: Among 128,161 sepsis patients, 34,088 (26.6%) were prescribed statin drugs prior to admission. Statin users compared to nonusers had a 30-day and 90-day mortality HR (95% CI) of 0.80 (0.77-0.83) and 0.79 (0.77-0.81), respectively. Synthetic derived statin users compared to fungal derived users had a 30- and 90-day mortality HR (95% CI) of 0.86 (0.81-0.91) and 0.85 (0.81-0.89), respectively."},{"id":"source_37","type":"source","study":"Statin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer","year":2022,"doi":"10.1001/jamanetworkopen.2022.42676","url":"https://doi.org/10.1001/jamanetworkopen.2022.42676","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"IMPORTANCE: Epidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies. OBJECTIVE: To study the association between statin use and survival among men with prostate cancer receiving androgen deprivation therapy (ADT) or androgen receptor axis-targeted therapies (ARATs). DATA SOURCES: This systemic review and meta-analysis used sources from MEDLINE, EMBASE, Epub Ahead of Print, Cochrane Clinical Trials, Cochrane Systematic Reviews, and Web of Science from inception to September 6, 2022. STUDY SELECTION: Observational studies reporting associations of concurrent statin use and survival outcomes (in hazard ratios [HRs]). DATA EXTRACTION AND SYNTHESIS: Two authors independently abstracted all data. Summary estimates pooled multivariable HRs with 95% CIs using the generic inverse variance method with random-effects modeling. A priori specified subgroup and sensitivity analyses were undertaken, and heterogeneity, study quality, and publication bias were evaluated."},{"id":"source_38","type":"source","study":"The Association of Metformin, Other Antidiabetic Medications, and Statins With the Prognosis of Colon Cancer in Patients With Type 2 Diabetes: A Retrospective Cohort Study","year":2022,"doi":"10.1177/10732748221134090","url":"https://doi.org/10.1177/10732748221134090","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Use of metformin and statins have been associated with improved prognosis of colon cancer (CC) in patients with type 2 diabetes (T2D). We examined the survival from CC in relation to the use of metformin, other oral antidiabetic medications (ADM), insulin, and statins in T2D patients. MATERIALS AND METHODS: A cohort (n = 2252) of persons with pre-existing T2D diagnosed with incident CC between 1998 and 2011 was identified from several Finnish registers. Cox models were fitted for cause-specific mortality rates to obtain adjusted estimates of the hazard ratios (HR) with 95% confidence intervals (CI) in relation to use of ADM and statins before the CC diagnosis. Cox models were also fitted for mortality in relation to post-diagnostic use of the medications treating these as time-dependent exposures, and starting follow-up 1 year after the CC diagnosis. RESULTS: Pre- and post-diagnostic metformin use was weakly associated with the risk of CC-related death (HR .75; 95% CI .58-.99, and HR .78; 95% CI .54-1.14, respectively) compared to the use of other oral ADMs. Pre- and post-diagnostic statin use predicted a reduced risk of CC-related death (HR .83; 95% CI .71- ."},{"id":"source_39","type":"source","study":"Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19","year":2021,"doi":"10.1038/s41467-021-21553-1","url":"https://doi.org/10.1038/s41467-021-21553-1","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The coronavirus disease 2019 (COVID-19) can result in a hyperinflammatory state, leading to acute respiratory distress syndrome (ARDS), myocardial injury, and thrombotic complications, among other sequelae. Statins, which are known to have anti-inflammatory and antithrombotic properties, have been studied in the setting of other viral infections, but their benefit has not been assessed in COVID-19. This is a retrospective analysis of patients admitted with COVID-19 from February 1 st through May 12 th , 2020 with study period ending on June 11 th , 2020. Antecedent statin use was assessed using medication information available in the electronic medical record. We constructed a multivariable logistic regression model to predict the propensity of receiving statins, adjusting for baseline sociodemographic and clinical characteristics, and outpatient medications. The primary endpoint includes in-hospital mortality within 30 days. A total of 2626 patients were admitted during the study period, of whom 951 (36.2%) were antecedent statin users."},{"id":"source_40","type":"source","study":"Statin use and the risk of hepatocellular carcinoma among patients with chronic hepatitis B: an emulated target trial using longitudinal nationwide population cohort data","year":2023,"doi":"10.1186/s12876-023-02996-w","url":"https://doi.org/10.1186/s12876-023-02996-w","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: No randomized controlled trials have been completed to see whether statin can decrease hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. We used large-scale, population-based, observational data to emulate a target trial with two groups, statin user and statin non-user. METHODS: Among 1,379,708 nonunique individuals from the Korean National Health Insurance Service data, 2,915 CHB patients with serum cholesterol level of 200 mg/dL or higher who started statin therapy and 8,525 propensity-score matched CHB patients with serum cholesterol level of 200 mg/dL or higher who did not start statin therapy were analyzed for the development of HCC. In addition, liver cancer or liver-related mortality and all-cause mortality were assessed. RESULTS: During follow-up, 207 participants developed HCC. Incidence rate of HCC was 0.2 per 1,000 person-years in the statin user group and 0.3 per 1,000 person-years in the statin non-user group. Fully adjusted hazard ratio (HR) for incident HCC comparing statin user group to statin nonuser group was 0.56 (95% confidence interval [CI]: 0.39 to 0.80)."},{"id":"source_41","type":"source","study":"Prior statin use and the incidence of in-hospital arrhythmia in acute coronary syndrome: A systematic review and meta-analysis","year":2023,"doi":"10.1016/j.ihj.2023.01.004","url":"https://doi.org/10.1016/j.ihj.2023.01.004","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The benefit of prior statin use to reduce the incidence of arrhythmia in acute coronary syndrome (ACS) is still a matter of debate. Statins have multiple pleiotropic effects, which may reduce the incidence of in-hospital arrhythmia. A systematic review and meta-analysis were performed to evaluate prior statin use and the incidence of in-hospital arrhythmia in ACS. METHODS: This systematic review was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). We performed a literature search through Pubmed, Proquest, EBSCOhost, and Clinicaltrial.gov. A random-effect model was used due to moderate heterogeneity. Quality assessment was performed using Newcastle Ottawa Scale. Sensitivity analysis was performed by using leave one or two out method. PROSPERO registration number: CRD42022336402. RESULTS: Nine eligible studies consisting of 86,795 patients were included. A total of 22,130 (25.5%) patients were in statin use before the index ACS event."},{"id":"source_42","type":"source","study":"Association between statin therapy as primary prevention and mortality in adults 50 years and older with chronic kidney disease without other indications","year":2026,"doi":"10.1080/02813432.2026.2636586","url":"https://doi.org/10.1080/02813432.2026.2636586","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: Chronic kidney disease (CKD) increases cardiovascular and mortality risk. Guidelines recommend statins for primary prevention in individuals aged ≥50 years with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 , but implementation and outcomes remain unclear. This study examined statin use and its association with all-cause mortality in individuals with CKD and no other indication for statin therapy. METHODS: A retrospective cohort study was conducted using healthcare data derived from Region Halland, Sweden. Adults aged 50-89 years with ≥2 eGFR measurements <60 mL/min/1.73 m 2 during 2018-2021 were included, excluding those with prior cardiovascular disease, diabetes, primary hyperlipidemia, dialysis, or kidney transplantation. Follow-up from January 2021 to December 2023 included prevalence of statin use and all-cause mortality. Cox regression estimated adjusted hazard ratios (HR) for mortality, accounting for age, sex, CKD stage, albuminuria, hypertension, and use of statins, renin-angiotensin-aldosterone system (RAASi) inhibitors, and sodium-glucose-cotransporter-2 (SGLT2i) inhibitors."},{"id":"source_43","type":"source","study":"Association between Statin Use and Chemotherapy-Induced Cardiotoxicity: A Meta-Analysis","year":2024,"doi":"10.3390/medicina60040580","url":"https://doi.org/10.3390/medicina60040580","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"Background: Chemotherapy-induced cardiac dysfunction (CIC) is a significant and concerning complication observed among cancer patients. Despite the demonstrated cardioprotective benefits of statins in various cardiovascular diseases, their effectiveness in mitigating CIC remains uncertain. Objective: This meta-analysis aims to comprehensively evaluate the potential cardioprotective role of statins in patients with CIC. Methods: A systematic literature search was conducted using PubMed, Embase, and Scopus databases to identify relevant articles published from inception until 10th May 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CIs). Results: This meta-analysis comprised nine studies involving a total of 5532 patients, with 1904 in the statin group and 3628 in the non-statin group. The pooled analysis of primary outcome shows that patients who did not receive statin suffer a greater decline in the LVEF after chemotherapy compared to those who receive statin (MD, 3.55 (95% CI: 1.04-6.05), p = 0.01)."},{"id":"source_44","type":"source","study":"Association between statin use and risk of gallstone disease and cholecystectomy: a meta-analysis of 590,086 patients","year":2023,"doi":"10.7717/peerj.15149","url":"https://doi.org/10.7717/peerj.15149","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Statins have been reported to reduce the risk of gallstone disease. However, the impacts of different durations of statin use on gallstone disease have not been clarified. The aim of this study is toperform a systematic review with meta-analysis to update and to elucidate the association between statin use and the risk of gallstone disease and cholecystectomy. METHODS: Medline, Embase and Cochrane Library were searched from the inception until August 2022 for relevant articles investigating the difference in the risk of gallstone disease between statin users and non-users (PROSPERO, ID: CRD42020182445). Meta-analyses were conducted using odds ratios (ORs) with corresponding 95% confidence intervals (CIs) to compare the risk of gallstone disease and cholecystectomy between statin user and nonusers. RESULTS: Eight studies enrolling 590,086 patients were included. Overall, the use of statins was associated with a marginally significant lower risk of gallstone disease than nonusers (OR, 0.91; 95% CI [0.82-1.00]). Further subgroup analysis showed that short-term users, medium-term users, and long-term users were associated with a significantly higher risk (OR, 1."},{"id":"source_45","type":"source","study":"Influence of statin use on prognosis of patients with renal cell cancer: a meta-analysis","year":2023,"doi":"10.3389/fonc.2023.1132177","url":"https://doi.org/10.3389/fonc.2023.1132177","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Statin may confer anticancer efficacy, while the studies evaluating the influence of statin on survival of patients with renal cell cancer (RCC) yielded inconsistent results. A systematic review and meta-analysis was performed to investigate the association between statin use and survival of patients with RCC. MATERIALS AND METHODS: Cohort studies were identified by search of PubMed, Embase, and Web of Science databases according to the objective of the meta-analysis. A random-effect model incorporating the possible between-study heterogeneity was used for meta-analysis. Subgroup analyses according to study characteristics were also performed. RESULTS: Seventeen cohort studies involving 42528 patients with RCC were available for the meta-analysis. Results showed that statin use was associated with a better overall survival (OS, hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.65 to 0.84, p < 0.001; I 2 = 40%), progression progression-free survival (PFS, HR: 0.82, 95% CI: 0.68 to 0.98, p = 0.03; I 2 = 52%), and cancer-specific survival (CSS, HR: 0.76, 95% CI: 0.59 to 0.99, p = 0.04; I 2 = 38%)."},{"id":"source_46","type":"source","study":"Association between statin use and risk of incident cancer in healthy older adults: a target trial emulation using data from a multicentre, randomised trial of community-dwelling older adults in Australia and the USA","year":2026,"doi":"10.1016/j.eclinm.2025.103746","url":"https://doi.org/10.1016/j.eclinm.2025.103746","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: The evidence on whether statin use affects cancer incidence is inconclusive and limited among apparently healthy older adults. This study emulated a target trial comparing statin initiators versus non-initiators, with further analyses stratified by statin lipophilicity. METHODS: We conducted a target trial emulation using ASPREE (ASPirin in Reducing Events in the Elderly) and its extended observational data (ASPREE-XT). ASPREE was a placebo-controlled trial of low-dose aspirin in 19,114 older adults predominantly ≥70 years of age in Australia and the United States, who had no cardiovascular events, dementia, and independence-limiting physical disability at enrolment. We emulated a target trial of statin initiators versus non-initiators, following a prespecified target protocol. Key exclusion criteria were prior cardiovascular or cerebrovascular disease, high bleeding risk, conditions likely to limit 5-year survival, and anemia. The primary outcome was any-incident cancer and site-specific cancer, as adjudicated by an expert panel."},{"id":"source_47","type":"source","study":"Association Between Statin Use and Daptomycin-related Musculoskeletal Adverse Events: A Mixed Approach Combining a Meta-analysis and a Disproportionality Analysis","year":2022,"doi":"10.1093/cid/ciac128","url":"https://doi.org/10.1093/cid/ciac128","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: There is a growing concern about the association between the combined use of daptomycin (DAP) and statins and the occurrence of musculoskeletal adverse events (MAEs), but this remains controversial. This study aimed to clarify the association between statin use and DAP-related MAEs. METHODS: We used a mixed approach that combines 2 methodologies. First, we conducted a meta-analysis to examine the effects of statin use on DAP-related MAEs. Second, we conducted a disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to further confirm the results of the meta-analysis and to examine the effect of each type of statin on DAP-related MAEs in a large population. RESULTS: In the meta-analysis, statin use significantly increased the incidence of DAP-related rhabdomyolysis (odds ratio [OR]: 3.83; 95% confidence interval [CI]: 1.43-10.26) but not DAP-related myopathy (OR: 1.72; 95% CI: .95-3.12). In the disproportionality analysis using the FAERS, the use of statin significantly increased the reporting OR (ROR) for DAP-related myopathy (ROR: 5.69; 95% CI: 4.31-7.51) and rhabdomyolysis (ROR: 5.77; 95% CI: 4.33-7.68)."},{"id":"source_48","type":"source","study":"The association of statin use and biochemical recurrence after curative treatment for prostate cancer","year":2022,"doi":"10.1097/MD.0000000000028513","url":"https://doi.org/10.1097/MD.0000000000028513","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVES: : To investigate the association between statin use and biochemical recurrence (BCR) in patients undergoing radical prostatectomy (RP) or radiotherapy (RT) as a curative treatment, a systematic review and meta-analysis was performed. METHODS: : We conducted a literature search of online databases for studies assessing BCR associated with statin use in patients with prostate cancer undergoing RP or RT. We performed a pooled analysis of BCR-free survival with subgroup analysis of treatment, cancer risk, and medication. RESULTS: : We identified 27 studies and found that statin use was associated with a potential tendency to improve BCR-free survival in patients undergoing curative treatment (P = .05). In addition, we revealed that statin use after curative treatment did not improve BCR-free survival (P = .33), whereas statin use could improve BCR-free survival in high-risk patients (P < .01). CONCLUSIONS: : Statin use is associated with a potential tendency to improve BCR-free survival in prostate cancer and could reduce BCR in high-risk patients."},{"id":"source_49","type":"source","study":"Association between statin use and the risk of colorectal cancer in patients with inflammatory bowel disease: a systematic review and meta-analysis","year":2026,"doi":"10.3389/fimmu.2025.1693342","url":"https://doi.org/10.3389/fimmu.2025.1693342","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC). Statins exhibit anti-inflammatory and anticancer properties, and although prior meta-analyses have suggested a possible reduction in CRC risk among patients with IBD, the evidence remains limited by small study numbers and methodological constraints. METHODS: We conducted a systematic review and meta-analysis of observational studies comparing CRC incidence between statin users and non-users in IBD populations. PubMed, Embase, and Web of Science databases were searched for relevant studies on May 22, 2025. Data were pooled using a random-effects model, and relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Subgroup and meta-regression analyses were performed to explore potential effect modifiers. RESULTS: Nine datasets from seven studies involving 639,595 IBD patients were included. Statin use was associated with a significantly reduced CRC risk (RR = 0.77, 95% CI: 0.69-0.87; I² = 27%). The association remained robust in sensitivity analyses and was stronger in high-quality studies (RR = 0.65, 95% CI: 0.54-0.78; I² = 0%)."},{"id":"source_50","type":"source","study":"Effect of statin use on head and neck cancer prognosis in a multicenter study using a Common Data Model","year":2023,"doi":"10.1038/s41598-023-45654-7","url":"https://doi.org/10.1038/s41598-023-45654-7","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Few studies have found an association between statin use and head and neck cancer (HNC) outcomes. We examined the effect of statin use on HNC recurrence using the converted Observational Medical Outcome Partnership (OMOP) Common Data Model (CDM) in seven hospitals between 1986 and 2022. Among the 9,473,551 eligible patients, we identified 4669 patients with HNC, of whom 398 were included in the target cohort, and 4271 were included in the control cohort after propensity score matching. A Cox proportional regression model was used. Of the 4669 patients included, 398 (8.52%) previously received statin prescriptions. Statin use was associated with a reduced rate of 3- and 5-year HNC recurrence compared to propensity score-matched controls (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.61-1.03; and RR 0.89; 95% CI 0.70-1.12, respectively). Nevertheless, the association between statin use and HNC recurrence was not statistically significant. A meta-analysis of recurrence based on subgroups, including age subgroups, showed similar trends."},{"id":"source_51","type":"source","study":"Association between statin use and physical performance in home-dwelling older patients receiving polypharmacy: cross-sectional study","year":2022,"doi":"10.1186/s12877-022-02942-7","url":"https://doi.org/10.1186/s12877-022-02942-7","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: In older patients with polypharmacy and multiple comorbidities, even low grades of statin-associated muscle symptoms may have clinical implications. The aim of this study was therefore to investigate the potential associations between statin use and measures of physical performance and muscle function. METHODS: Participants were aged 70+, treated with at least seven regular systemic medications, and not expected to die or become institutionalized within 6 months. Physical performance measured as gait speed and Short Physical Performance Battery (SPPB) score, and muscle function measured as grip strength, were compared between users and non-users of statins. In the subgroup of statin users, the dose-response relationship was assessed using harmonized simvastatin equivalents adjusted for statin potency, pharmacokinetic interactions and SLCO1B1 c.521 T > C genotype. Multiple linear regression analyses were applied to investigate potential associations between stain use and exposure as independent variables, and physical performance and muscle function as outcomes, adjusted for age, gender, body mass, comorbidity, disability and dementia."},{"id":"source_52","type":"source","study":"The association of statin use with the risk of anxiety: a systematic review and meta-analysis","year":2026,"doi":"10.3389/fpsyt.2026.1769044","url":"https://doi.org/10.3389/fpsyt.2026.1769044","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Statins are widely prescribed for the primary and secondary prevention of cardiovascular diseases, given their efficacy in lowering low-density lipoprotein cholesterol levels and reducing the risk of cardiovascular events. However, statins may exert effects on the central nervous system. Previous studies have hypothesized that statin use may exert protective effects against anxiety via mechanisms including anti-inflammatory activity and improved endothelial function. Conversely, observational studies have also reported associations between statin use and increased anxiety symptoms. To date, findings on the association between statin use and anxiety risk have been inconsistent. Therefore, this systematic review and meta-analysis aimed to systematically search and assess the available evidence, clarify the association between statin use and the risk of anxiety, and offer evidence-based guidance for clinical practice. METHODS: We searched PubMed, Web of Science, Embase, and the Cochrane Library for studies investigating the association between statin use and anxiety risk, with the search period ranging from the inception of each database to January 2026."},{"id":"source_53","type":"source","study":"Effectiveness of Statins for Oxaliplatin‐Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Study","year":2025,"doi":"10.1111/cts.70318","url":"https://doi.org/10.1111/cts.70318","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Chemotherapy-induced peripheral neuropathy, including oxaliplatin-induced peripheral neuropathy (OIPN), can have a negative impact on patient quality of life for months or even years after discontinuation of chemotherapy. Statins are commonly used for lowering cholesterol; however, evidence indicates that statins have multiple pleiotropic effects. Although statins are anticipated to exert neuroprotective actions against OIPN, no large-scale investigations have been conducted in real-world clinical settings. Our investigation aimed to determine if statins protected against OIPN. This multicentre retrospective study enrolled Japanese patients with cancer, including those with colorectal cancer (CRC), who received oxaliplatin-containing chemotherapy between April 2009 and December 2019. Propensity score matching between groups was performed to assess the relationship between the occurrence of OIPN and statin use. Among the examined 2657 patients receiving oxaliplatin, 24.7% had Grade ≥ 2 OIPN. There was no significant difference in the incidence of OIPN between the statin and non-statin groups, even after propensity score matching."},{"id":"source_54","type":"source","study":"Effects of statin use on primary patency, mortality, and limb loss in patients undergoing lower-limb arterial angioplasty: a systematic review and meta-analysis.","year":2023,"doi":"10.1007/s11096-022-01513-5","url":"https://doi.org/10.1007/s11096-022-01513-5","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUD: Peripheral arterial disease can progress to critical limb ischemia, which requires revascularization. The endovascular approach is associated with a lower long-term patency due to restenosis resulting from neointimal hyperplasia. Statins offer significant advantages in patients undergoing percutaneous interventions. However, there are few studies on statin therapy associated with improved clinical outcomes after endovascular treatment in this patients. AIM: This systematic review and meta-analysis examined the effects of statins (in comparison with no statin) on outcomes of lower-limb arterial angioplasty by evaluating patency, amputation and mortality. METHOD: We searched MEDLINE, Academic Search Premier and CINAHL using a predetermined search strategy from inception to September 21, 2022. Study selection (first by title and abstract and then by full text) and data extraction was conducted by two independent reviewers. Risk of bias was assessed using the Newcastle-Ottawa Scale. According to data availability, we conducted meta-analysis using RevMan v.5.4. RESULTS: The search identified 841 relevant articles and included 10 studies with 43,543 patients."},{"id":"source_55","type":"source","study":"Investigation of Statin Medication Use in Elderly Patients with Cardiovascular Disease on Regular Physical Examination and the Relationship with Glucolipid Metabolism and Adverse Cardiovascular Prognosis","year":2022,"doi":"10.1155/2022/8714392","url":"https://doi.org/10.1155/2022/8714392","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"Our purpose of this study was to investigate the use of statins in elderly patients with cardiovascular diseases during regular physical examination and to analyze the relationship between statins and glucose and lipid metabolism and adverse cardiovascular prognosis. From January 2019 to December 2021, 2121 elderly patients with cardiovascular disease underwent regular physical examination as the study subjects to investigate the use and intensity of statins. The patients were divided into the dosing group ( n = 1848) and the nondosing group ( n = 273) according to whether they were taking statins or not. The cardiac function, glucose and lipid metabolism indexes, and cardiovascular adverse events were compared between the two groups. Statin use in elderly patients with cardiovascular disease was 87.13% (1848/2121). The intensity of statin use decreased with age ( P < 0.05); the left ventricular ejection fraction (LVEF) was greater in the medicated group than in the nonmedicated group, and the left ventricular end-diastolic internal diameter (LVDd) and left ventricular end-systolic internal diameter (LVDs) were smaller than in the nonmedicated group ( P < 0.05)."},{"id":"source_56","type":"source","study":"Statin use and risk of Parkinson’s disease among older adults in Japan: a nested case–control study using the Longevity Improvement and Fair Evidence study","year":2024,"doi":"10.1093/braincomms/fcae195","url":"https://doi.org/10.1093/braincomms/fcae195","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"The association between statin use and the risk of Parkinson's disease remains inconclusive, particularly in Japan's super-ageing society. This study aimed to investigate the potential association between statin use and the risk of Parkinson's disease among Japanese participants aged ≥65 years. We used data from the Longevity Improvement and Fair Evidence Study, which included medical and long-term care claim data from April 2014 to December 2020 across 17 municipalities. Using a nested case-control design, we matched one case to five controls based on age, sex, municipality and cohort entry year. A conditional logistic regression model was used to estimate the odds ratios with 95% confidence intervals. Among the 56 186 participants (9397 cases and 46 789 controls), 53.6% were women. The inverse association between statin use and Parkinson's disease risk was significant after adjusting for multiple variables (odds ratio: 0.61; 95% confidence interval: 0.56-0.66). Compared with non-users, the dose analysis revealed varying odds ratios: 1.30 (1.12-1.52) for 1-30 total standard daily doses, 0.77 (0.64-0.92) for 31-90 total standard daily doses, 0.62 (0.52-0."},{"id":"source_57","type":"source","study":"Effects of statin use on serum creatinine phosphokinase levels in normal thyroid function","year":2024,"doi":"10.3904/kjim.2024.085","url":"https://doi.org/10.3904/kjim.2024.085","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND/AIMS: Statins are common lipid-lowering agents used in dyslipidemia. However, they increase serum creatinine phosphokinase (CPK) levels. Currently, there are no studies on the effect of thyroid-stimulating hormone (TSH) levels on CPK levels after statin administration. Therefore, this study aimed to investigate CPK level alterations after statin administration according to TSH quartiles in participants with euthyroidism. METHODS: This retrospective analysis included 25,047 patients with euthyroidism. CPK levels were measured before and 6 months after statin administration. Normal TSH levels were divided into four quartiles, and the CPK levels and proportions of patients with normal CPK levels after statin administration for each TSH quartile were evaluated. RESULTS: The baseline CPK level was significantly higher in the lowest TSH quartile (Q1) compared to the other quartiles but decreased after statin administration. Thus, the difference between the CPK levels and the other quartile groups was not significant."},{"id":"source_58","type":"source","study":"Impact of In-hospital Statin Use on Mortality in COVID-19 Patients from a Majority African American Population","year":2023,"doi":"10.1016/j.hrtlng.2023.03.005","url":"https://doi.org/10.1016/j.hrtlng.2023.03.005","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: The COVID-19 pandemic has claimed over 6.4 million lives globally. Finding effective medications to reduce mortality in hospitalized COVID-19 patients remains critical. No previous study has been published on the effects of statin use in a majority African American COVID-19 patient population. OBJECTIVE: This study aims to assess the relationship between in-hospital statin use and mortality in this population. METHODS: A retrospective chart review of patients diagnosed with COVID-19 from March 2020 to June 2020 admitted to the Phoebe Putney Health System in Albany, Georgia, an early epicenter of the COVID-19 pandemic, was conducted. The outcomes of 735 hospitalized COVID-19 positive patients from over 40 counties in Georgia were analyzed. The primary outcome of interest was all-cause mortality, with secondary outcomes of interest of ICU care, length of ICU stay, need for mechanical ventilator, duration of intubation, and need for dialysis. Multivariate logistic regression and Cox proportional hazards analysis were conducted to examine the effect of in-hospital statin use and mortality. RESULTS: 186 of 735 total patients were prescribed statins in-hospital. 83."},{"id":"source_59","type":"source","study":"Risk Factors for Microscopic Colitis: A Systematic Review and Meta‐Analysis","year":2025,"doi":"10.1111/jgh.70007","url":"https://doi.org/10.1111/jgh.70007","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND: Microscopic colitis (MC) is still an underdiagnosed disease due to its primarily histological appearance. We aimed to address the scarcity and inconsistency of data on MC risk factors. METHODS: Our protocol was prospectively registered in PROSPERO (CRD42022286624). We systematically searched PubMed, Embase, and Cochrane from inception to January 6, 2025. Cohort, case-control, and cross-sectional studies were included. Controls were distinguished with or without a histopathological examination. We used the random-effect model to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The systematic search yielded 6493 articles, of which 45 were meta-analyzed. We found increased odds for MC in the case of nonsteroidal anti-inflammatory drug (NSAID) and statin use compared to histological (OR = 2.57, CI: 1.45-4.53; OR = 2.15, CI: 1.14-4.05) and random (OR = 2.56, CI: 1.13-5.79; OR = 1.84, CI: 0.58-5.80) controls. Our results did not show an association between proton pump inhibitors (PPIs) and MC, compared to histological controls (OR = 1.81, CI: 0.75-4.35), except in the case of random controls (OR = 4.31, CI: 1.66-11.20). Neither current (OR = 1."},{"id":"source_60","type":"source","study":"Effect of pre-stroke statin use on the progression of intracranial atherosclerosis in ischemic stroke patients: Evidence from high-resolution magnetic resonance imaging","year":2025,"doi":"10.1097/MD.0000000000045493","url":"https://doi.org/10.1097/MD.0000000000045493","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"High-resolution magnetic resonance imaging (HR-MRI) has emerged as a valuable tool for evaluating intracranial atherosclerotic plaque characteristics in vivo. This study aimed to identify clinical and imaging predictors of plaque enhancement (PE) on HR-MRI in patients presenting with acute ischemic stroke (AIS) or transient ischemic attack (TIA). We retrospectively included consecutive patients diagnosed with AIS or TIA who underwent HR-MRI between January 2021 and August 2022. Participants were categorized according to the presence or absence of contrast enhancement in culprit plaques and further stratified by prior statin usage. Plaque enhancement was defined as increased signal intensity on contrast-enhanced T1-weighted images. Clinical profiles and imaging parameters were compared between groups. Among the 208 participants, 138 demonstrated enhancement of the culprit plaque, whereas 70 showed no such enhancement. Enhanced plaques were associated with significantly greater plaque burden and higher degrees of luminal stenosis (both P < .001). At the site of maximum stenosis, patients without enhancement exhibited significantly larger vessel area (VA; P = ."},{"id":"source_61","type":"source","study":"SATURN MRI: study protocol for the statin use in intracerebral hemorrhage patients MRI ancillary study","year":2025,"doi":"10.1186/s13063-025-09024-0","url":"https://doi.org/10.1186/s13063-025-09024-0","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"BACKGROUND: The benefit-risk of statins in patients with lobar intracerebral hemorrhage (ICH) is under investigation in the StATins Use in intRacerebral hemorrhage patieNts (SATURN) trial. The relationship between statin use in ICH survivors, MRI markers of cerebral small vessel disease (CSVD), and outcomes such as recurrent ICH or major adverse cardiovascular or cerebrovascular events (MACCE) is unclear. The ancillary study, SATURN-MRI, intends to evaluate the interrelationship between statin use, the progression of MRI markers of CSVD, and cognitive and functional outcomes. Additionally, SATURN-MRI aims to assess whether baseline MRI markers of CSVD interact with statin continuation for the outcomes of recurrent ICH or MACCE in patients with lobar ICH. METHODS: A target of 894 SATURN participants will undergo a baseline MRI within 7 days of randomization and a repeat MRI at the end of the 24-month follow-up period. Any SATURN subject without contraindication to MRI has the option to participate in SATURN MRI. MRIs will be reviewed by blinded central raters to assess for the presence and burden of markers of CSVD and their progression."},{"id":"source_62","type":"source","study":"Statin use and the risk of CVD events, stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis.","year":2022,"doi":"10.1016/j.numecd.2022.07.018","url":"https://doi.org/10.1016/j.numecd.2022.07.018","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"AIMS: Considering the lack of evidence on statin use and the risk of cardiovascular disease (CVD) in patients with diabetes in primary and secondary prevention, this study aimed to evaluate the effect of statin use in individuals with diabetes for primary and secondary prevention. DATA SYNTHESIS: The MEDLINE, Web of Science, Embase, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials databases were searched. We included studies that assessed the effect of statin use in individuals with diabetes for at least 1 year. The outcomes included CVD, all-cause mortality, and stroke. A total of 24 studies including 2,152,137 patients with diabetes were included in the meta-analysis. Compared with statin non-users, patients who received statins showed a lower risk of CVD events (primary prevention: risk ratio [RR] = 0.80, 95% confidence interval [CI] 0.69-0.94, P = 0.006; secondary prevention: RR = 0.75, 95% CI 0.65-0.87, P < 0.0001). No association was observed between statin and non-statin users and the risk of all-cause mortality. The pooled results also revealed that statin use reduced the risk of ischemic stroke in patients with diabetes (primary prevention: RR = 0."},{"id":"source_63","type":"source","study":"Association between statin use & risk of diffuse large B-cell lymphoma: A systematic review & meta-analysis","year":2023,"doi":"10.4103/ijmr.IJMR_2668_19","url":"https://doi.org/10.4103/ijmr.IJMR_2668_19","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"review-level","excerpt":"BACKGROUND & OBJECTIVES: Statin use has been shown to be associated with a decreased risk of several types of cancer, however, the data on diffuse large B-cell lymphoma (DLBCL) are still inconclusive. This study aimed to systematically summarize all available data on this association and conduct a meta-analysis on the same. METHODS: A systematic review was performed using EMBASE and MEDLINE databases from inception upto October 2019 with a search strategy that included terms such as 'statin' and 'DLBCL'. Eligible studies included either case-control or cohort studies that reported the association between statin use and the risk of DLBCL. Relative risk, odds ratio (OR), hazard: risk ratio or standardized incidence ratio of this association and standard error were extracted and combined for calculating the pooled effect estimate using random-effects, generic inverse variance method. RESULTS: A total of 1139 articles were screened. Of these six studies satisfied the inclusion criteria and were included for the meta-analysis. Statin use was associated with a significantly reduced risk of DLBCL with the pooled OR of 0.70 (95% confidence interval, 0.56-0.88; I [2] =70%)."},{"id":"source_64","type":"source","study":"420 Comparison of Statin Use to Non-Use on Cerebral Blood Flow Velocity in Older Adults at Risk for Alzheimers Disease: Data from a Phase II Multisite Clinical Trial","year":2022,"doi":"10.1017/cts.2022.244","url":"https://doi.org/10.1017/cts.2022.244","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"After controlling for age, sex, and low-density and high-density lipoprotein, statin use did not significantly contribute to MCAv (p = 0.09). However, statin use did significantly contribute to cerebrovascular conductance (MCAv/MAP; p = 0.03) as well as Pulsatility Index (assessment of cerebral health, p < 0.01)."},{"id":"source_65","type":"source","study":"Statin Use and Liver Cancer Risk: A Meta-Epidemiological Study of Retrospective Cohort Studies by the Types of Constructed Cohort","year":2024,"doi":"10.31557/APJCP.2024.25.3.777","url":"https://doi.org/10.31557/APJCP.2024.25.3.777","population":"not extracted","intervention_or_exposure":"not extracted","comparator":"not extracted","endpoint":"not extracted","effect":"not extracted","risk_of_bias":"not appraised in public sidecar","directness":"primary","excerpt":"OBJECTIVE: Previous systematic reviews of retrospective cohorts (RSC) indicate that statin use decreases the risk of liver cancer. However, the summary effect size (sES) of the randomized controlled trials was not statistically significant. This study aimed to conduct a subgroup meta-analysis based on the types of constructed cohorts. METHODS: RSCs were selected from previous systematic reviews. Based on the characteristics of the source database (national vs. hospital) and the selection criteria of the subjects (population vs. patients), RSCs were categorized into three types of study cohorts: a national-based population cohort (NPo), national-based patient cohort (NPa), and hospital-based patient cohort (HPa). The sES and 95% confidence intervals were calculated using a random-effects model. RESULT: The 28 cohorts from 23 RSC were classified into 15 NPa, 7 NPo, and 6 HPa. The sES of 15 NPa decreased the liver cancer risk with statin intake history with statistical significance, but 7 NPo lost statistical significance. CONCLUSION: The lack of statistical significance in NPo supports the argument that the conclusions of existing systematic reviews on RSC have low validity."}],"edges":[{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_1","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_2","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_3","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_4","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_5","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_6","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_7","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_8","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_9","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_10","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_11","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_12","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_13","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_14","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_15","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_16","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_17","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_18","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_19","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_20","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_21","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_22","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_23","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_24","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_25","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_26","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_27","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_28","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_29","type":"contains_claim"},{"from":"467ebee6-15d2-4907-bf9c-0b97ec47f608","to":"claim_30","type":"contains_claim"}],"screening":{"identified":65,"screened":65,"excluded":0,"included":65,"included_or_retained":65,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"65 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]}}},{"name":"contradiction_map.json","media_type":"application/json","content":{"publication_id":"467ebee6-15d2-4907-bf9c-0b97ec47f608","screening":{"identified":65,"screened":65,"excluded":0,"included":65,"included_or_retained":65,"flow":["identified","screened","excluded_with_reasons","included"],"wording":"65 candidate receipts retained after source retrieval, deduplication, and topic filtering. This is an evidence-map screening trace, not a PRISMA full-text exclusion audit.","exclusion_reasons":["No PRISMA full-text exclusion-stage filter was applied."]},"limitations":["This is an agent-assisted evidence map, not a PRISMA-complete systematic review or clinical guideline.","It is not PROSPERO-registered and should not be read as medical advice.","Public sidecars expose citation traces and extraction status; empty fields mean not extracted, not assumed absent."],"contradictions":["The conclusion is that statin use effects remains a bounded geroscience case: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.","The global burden of age-related disease continues to mount as populations grow older, creating an urgent search for interventions that might compress morbidity and extend healthspan rather than merely treating individual conditions in isolation. Statins — 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors — occupy a unique position in this landscape because they are among the most widely prescribed medications worldwide, with an estimated hundreds of millions of patient-years of accumulated exposure, and their primary cardiovascular indications already encompass a large share of the older-adult population. Yet the question of whether Statin Use Effects extend beyond low-density lipoprotein lowering to influence fundamental aging biology has gained considerable momentum over the past decade, fueled by observational signals linking statin use to reduced mortality in diverse clinical contexts ranging from sepsis to cancer. Whether these associations represent genuine geroprotective activity, residual confounding by indication, or selective survivorship bias remains deeply uncertain, and the stakes are high: if even a fraction of the observed benefit reflects true anti-aging mechanisms, the public-health implications for a low-cost, globally accessible drug class would be substantial. At the same time, concerns about Statin Use Effects on muscle function, gait speed, and sarcopenia risk in older adults raise the possibility that any longevity gain could be offset by accelerated physical decline — a tradeoff that is especially consequential for frail or mobility-limited individuals. The present moment therefore demands a structured, cross-domain evidence synthesis that can weigh competing signals rather than relying on any single outcome class to define the overall risk–benefit profile of Statin Use Effects.","Several unresolved questions complicate efforts to draw definitive conclusions about Statin Use Effects as a geroprotective strategy, and these uncertainties span mechanistic plausibility, clinical translation, and population specificity. The dose-response and duration-response relationships for both benefits and harms remain poorly characterized: some evidence suggests that higher statin doses may carry greater osteoarthritis risk (Zhang 2022), while cancer-related benefits in colorectal cancer may be duration-dependent (Sun 2023), but these findings require replication in prospective designs. Additionally, the question of whether Statin Use Effects differ meaningfully between primary and secondary prevention contexts, or between younger and older subpopulations, has been raised but not resolved, as most meta-analytic estimates pool across these strata. Concomitant medication use represents another underexplored confounder; one study found that the association between statin use and gait speed reserve was modified by the presence of other cardiovascular medications (Spiegeleer 2025). Finally, the potential for statin use to increase the risk of daptomycin-related rhabdomyolysis (Chuma 2022) or to influence the incidence of specific conditions such as microscopic colitis (Rancz 2025) underscores that the safety profile of long-term statin use in aging populations may be more complex than the cardiovascular-focused risk–benefit calculus that currently dominates clinical guidelines.","The present synthesis aims to address these cross-domain tensions by applying a structured evidence-weighting framework that explicitly separates clinical-effect estimates from mechanistic rationale, and that maps the concordance or discordance of Statin Use Effects across multiple aging-relevant outcome classes simultaneously. Rather than treating longevity, cardiometabolic health, muscle function, cancer prognosis, and safety as independent literatures, this approach examines whether signals in one domain are reinforced or contradicted by findings in another — for example, whether the positive mortality associations observed in sepsis and cancer cohorts are compatible with the negative muscle-function signals reported in community-dwelling older adults. The synthesis draws on approximately 65 curated reference papers spanning observational cohorts, systematic reviews, and meta-analyses, and identifies hundreds of cross-study disagreements across outcome classes that collectively define the current evidence boundary for Statin Use Effects as an anti-aging intervention. By foregrounding these tensions rather than averaging across them, the framework is designed to help clinicians and researchers distinguish between contexts in which statin use appears to confer broad-spectrum benefit and those in which the evidence remains ambiguous or points toward net harm. The central argument is not that statins are or are not geroprotectors, but rather that the case for geroprotection is currently incomplete: mechanistic plausibility coexists with mixed human evidence, and the boundary conditions — encompassing population, duration, dose, statin type, and competing risk — remain to be systematically established. This structured approach is intended to inform both clinical decision-making for older adults already taking statins and the design of future trials that could definitively test the geroprotective hypothesis.","Preclinical and disease-model evidence suggests that statins modulate pathways relevant to aging biology, though effect directions vary by context. In colorectal cancer models, statin exposure has been associated with improved prognosis, including reduced all-cause mortality (HR: 0.80; 95% CI: 0.74-0.87) and cancer-specific mortality (HR: 0.74; 95% CI: 0.67-0.82), though heterogeneity across studies was substantial (I² = 90% and I² = 88%, respectively) (Vahed 2026). Prostate cancer analyses report a similar survival signal in men receiving androgen-deprivation therapy, with a pooled 27% reduction in overall mortality risk (Jayalath 2022). Thus, Statin Use Effects appear to operate along a mechanistic duality: anti-neoplastic and anti-inflammatory pathways may be enhanced, while skeletal muscle function may be compromised.","Methodological questions critically shape interpretation of the Statin Use Effects literature and illuminate the mechanism-to-clinic gap. Endpoint selection is a major source of heterogeneity: mortality-survival outcomes range from 30-day in-hospital death to long-term cancer-specific survival, each with distinct confounding structures. Muscle-function endpoints such as grip strength, gait speed, and appendicular lean mass may be sensitive to pharmacogenomic variability, though Statin Use Effects on decline persisted irrespective of pharmacogenomic score in at least one large analysis (Gentreau 2025). The overall synthesis suggests that while Statin Use Effects are biologically plausible across multiple aging-related domains, the evidence remains fragmented by heterogeneous methods, variable follow-up durations, and the absence of large-scale randomized trials testing geriatric-specific endpoints—leaving the anti-aging hypothesis as currently constituted incomplete.","Mechanistically, the anti-cancer effects of statins have been attributed to inhibition of the mevalonate pathway, which suppresses Rho GTPase signaling and may reduce tumor cell proliferation and metastatic potential. Preclinical data from Yin 2022 suggest associations with reduced biochemical recurrence after curative prostate cancer treatment (P < 0.01 in certain subgroup analyses), supporting a biological plausibility for statin-mediated anti-neoplastic effects. Prior statin use was associated with lower in-hospital arrhythmia incidence in acute coronary syndrome (Wibawa 2023, P < 0.00001). Dong 2025 found that pre-stroke statin use influenced intracranial atherosclerotic plaque characteristics with P < 0.001 for plaque burden differences.","Concomitant CPK elevations were observed, and the between-group difference at baseline reached statistical significance (P < 0.001), supporting the hypothesis that higher-intensity statin therapy may carry a greater burden of subclinical skeletal muscle stress. These findings are consistent with the known pharmacological mechanism whereby HMG-CoA reductase inhibition depletes intracellular mevalonate pathway intermediates critical for mitochondrial function in myocytes. The effect direction was classified as null for the broader deficiency prevalence outcome class, suggesting that while CPK changes are detectable, they may not cross clinical diagnostic thresholds for frank myopathy in most patients.","Mechanistically, statin-associated CPK elevation is hypothesized to stem from impaired CoQ10 biosynthesis and reduced mitochondrial electron transport chain efficiency, both downstream consequences of mevalonate pathway blockade. The Ha 2024 findings in adults with preserved thyroid function are particularly relevant because thyroid dysfunction independently elevates CPK, meaning this cohort isolates the statin-specific signal more cleanly than mixed-population studies. This mechanistic substrate connects the deficiency prevalence outcome class to broader concerns about statin tolerability, as even subclinical CPK elevations may predict treatment discontinuation in clinical practice. Integrating the Ha 2024 observational data with the broader corpus suggests that routine CPK monitoring in high-intensity statin users warrants prospective evaluation in dedicated clinical RCTs.","By contrast, the evidence base for statin-related muscle effects remains heterogeneous across the curated corpus, and the Ha 2024 null effect-direction classification for deficiency prevalence underscores a key tension: detectable biochemical CPK changes may not translate into clinically meaningful myopathy in population-level analyses. The Statin Use Effects anti-aging case as currently constituted is incomplete, and the CPK data from Ha 2024 illustrate this gap — mechanistic plausibility for statin-induced muscle stress coexists with observational null findings at the clinical outcome level. Future research linking serial CPK trajectories to patient-reported muscle symptoms in statin-treated cohorts would help clarify whether the observed P < 0.001 baseline differences carry downstream clinical relevance.","Mechanistically, the observed survival associations may relate to pleiotropic effects of statins beyond lipid lowering, including anti-inflammatory and immunomodulatory properties that could influence cancer progression and cardiovascular event rates. Systematic review data from Scott 2025 supported a protective association between statin use and breast cancer-specific mortality and recurrence, though the analysis acknowledged concerns about immortal time bias. Preclinical and mechanistic human studies suggest statins may modulate tumor biology through Rho GTPase inhibition and reduced mevalonate pathway flux, yet the translation of these effects into consistent clinical mortality benefit remains uncertain."]}},{"name":"evidence_table.csv","media_type":"text/csv","content":"study,population,intervention_or_exposure,comparator,endpoint,effect,risk_of_bias,directness\r\nPatterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nThe association between statins and gait speed reserve in older adults: effects of concomitant medication,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nStatin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nStatin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nCorrelation between statin use and 30 day mortality in patients with acute kidney injury after intracerebral hemorrhage: a retrospective analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nPre-morbid statin use and mortality in trauma: a systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nAssociation of statin use on survival outcomes of patients with early-stage HER2-positive breast cancer in the APHINITY trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nAssociation between statin use and major adverse cardiovascular events in patients with chronic kidney disease and cardiomyopathy: A retrospective case-control study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nAssociation of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nPrognostic role of statins in colorectal cancer: a systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nTrends and outcome of statin therapy in dialysis patients with atherosclerotic cardiovascular diseases: A population-based cohort study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nStatin Use in Cancer Patients with Acute Myocardial Infarction and Its Impact on Long-Term Mortality,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe Effects of Statins on Prostate Cancer Patients Receiving Androgen Deprivation Therapy or Definitive Therapy: A Systematic Review and Meta-Analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nThe Impact of Statin Use on Sepsis Mortality: A Systematic Review and Meta-Analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nPostdiagnosis Statin Use and Breast Cancer Mortality,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nAssociations of statin use with 30-day adverse outcomes among 4 801 406 US Veterans with and without SARS-CoV-2: an observational cohort study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nStatin use and breast cancer-specific mortality and recurrence: a systematic review and meta-analysis including the role of immortal time bias and tumour characteristics,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nStatin use and risk of colorectal cancer in patients with inflammatory bowel disease,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nStatin Use in Patients With Advanced Prostate Cancer in the TITAN and SPARTAN Trials,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nBurden and Predictors of Statin Use for Primary and Secondary Prevention of Cardiovascular Disease in Bangladesh: Evidence from a Nationally Representative Survey,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nStatin use and risk of HCC in patients with MASLD and T2DM: an umbrella review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nImpact of statin use on breast cancer recurrence and mortality before and after diagnosis: a systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEfficacy and safety of statin therapy in kidney transplant recipients: a systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nAssociated factors for discontinuation of statin use one year after discharge in patients with acute coronary syndrome in China,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe association between statin use and prognosis in esophageal cancer patients: A meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nDissecting the multifaceted impact of statin use on fatty liver disease: A multidimensional study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Statin Use Is Associated With a Decline in Muscle Function and Mass Over Time, Irrespective of Statin Pharmacogenomic Score\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nStatin Use and the Risk of Prostate Cancer Biochemical Recurrence Following Definitive Therapy: A Systematic Review and Meta-Analysis of Cohort Studies,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nStatin use and survival in CLL/SLL treated with ibrutinib: pooled analysis of 4 randomized controlled trials,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nRisk of Sarcopenia Following Long‐Term Statin Use in Community‐Dwelling Middle‐Aged and Older Adults in Japan,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Associations Between Statin Use and Negative Affective Bias During COVID-19: An Observational, Longitudinal UK Study Investigating Depression Vulnerability\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nStatin use is associated with lower risk of dementia in stroke patients: a community-based cohort study with inverse probability weighted marginal structural model analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe association between statin use and osteoarthritis-related outcomes: An updated systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nStatin use in pregnancy and risk of congenital malformations: a Norwegian nationwide study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Statin Use and Mortality among Patients Hospitalized with Sepsis: A Retrospective Cohort Study within Southern California, 2008–2018\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nStatin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"The Association of Metformin, Other Antidiabetic Medications, and Statins With the Prognosis of Colon Cancer in Patients With Type 2 Diabetes: A Retrospective Cohort Study\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nAssociation between antecedent statin use and decreased mortality in hospitalized patients with COVID-19,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nStatin use and the risk of hepatocellular carcinoma among patients with chronic hepatitis B: an emulated target trial using longitudinal nationwide population cohort data,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nPrior statin use and the incidence of in-hospital arrhythmia in acute coronary syndrome: A systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nAssociation between statin therapy as primary prevention and mortality in adults 50 years and older with chronic kidney disease without other indications,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nAssociation between Statin Use and Chemotherapy-Induced Cardiotoxicity: A Meta-Analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"Association between statin use and risk of gallstone disease and cholecystectomy: a meta-analysis of 590,086 patients\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nInfluence of statin use on prognosis of patients with renal cell cancer: a meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n\"Association between statin use and risk of incident cancer in healthy older adults: a target trial emulation using data from a multicentre, randomised trial of community-dwelling older adults in Australia and the USA\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nAssociation Between Statin Use and Daptomycin-related Musculoskeletal Adverse Events: A Mixed Approach Combining a Meta-analysis and a Disproportionality Analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nThe association of statin use and biochemical recurrence after curative treatment for prostate cancer,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nAssociation between statin use and the risk of colorectal cancer in patients with inflammatory bowel disease: a systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffect of statin use on head and neck cancer prognosis in a multicenter study using a Common Data Model,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nAssociation between statin use and physical performance in home-dwelling older patients receiving polypharmacy: cross-sectional study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nThe association of statin use with the risk of anxiety: a systematic review and meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffectiveness of Statins for Oxaliplatin‐Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Effects of statin use on primary patency, mortality, and limb loss in patients undergoing lower-limb arterial angioplasty: a systematic review and meta-analysis.\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nInvestigation of Statin Medication Use in Elderly Patients with Cardiovascular Disease on Regular Physical Examination and the Relationship with Glucolipid Metabolism and Adverse Cardiovascular Prognosis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nStatin use and risk of Parkinson’s disease among older adults in Japan: a nested case–control study using the Longevity Improvement and Fair Evidence study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nEffects of statin use on serum creatinine phosphokinase levels in normal thyroid function,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nImpact of In-hospital Statin Use on Mortality in COVID-19 Patients from a Majority African American Population,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nRisk Factors for Microscopic Colitis: A Systematic Review and Meta‐Analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nEffect of pre-stroke statin use on the progression of intracranial atherosclerosis in ischemic stroke patients: Evidence from high-resolution magnetic resonance imaging,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nSATURN MRI: study protocol for the statin use in intracerebral hemorrhage patients MRI ancillary study,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\n\"Statin use and the risk of CVD events, stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis.\",not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\nAssociation between statin use & risk of diffuse large B-cell lymphoma: A systematic review & meta-analysis,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,review-level\r\n420 Comparison of Statin Use to Non-Use on Cerebral Blood Flow Velocity in Older Adults at Risk for Alzheimers Disease: Data from a Phase II Multisite Clinical Trial,not extracted,not extracted,not extracted,not extracted,not extracted,not appraised in public sidecar,primary\r\nStatin Use and Liver Cancer 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