Evidence Trace, complete trial record
In plain terms
In plain terms: Statins (simvastatin, pravastatin, atorvastatin, rosuvastatin) has strong evidence from human clinical trials. The benefit shown in those trials is death and major cardiovascular events in people with coronary heart disease or other vascular disease (a). heart attack, stroke and cardiovascular death in people without cardiovascular disease at raised risk (a). cardiovascular events in adults 70 and over without cardiovascular disease (b, one trial). disability-free survival in adults 70 and over (d, tested, no benefit). preventing dementia and cognitive decline (d, tested, no benefit). no trial has tested statins for longevity in healthy, low-risk adults if that describes your situation.
Statins (simvastatin, pravastatin, atorvastatin, rosuvastatin)
A
Replicated: replicated trials on a qualifying endpoint
The endpoint this grade is based on: Hard clinical endpoint (mortality, major event), Death and major cardiovascular events in people with coronary heart disease or other vascular disease (A). Heart attack, stroke and cardiovascular death in people without cardiovascular disease at raised risk (A). Cardiovascular events in adults 70 and over without cardiovascular disease (B, one trial). Disability-free survival in adults 70 and over (D, tested, no benefit). Preventing dementia and cognitive decline (D, tested, no benefit). No trial has tested statins for longevity in healthy, low-risk adults.
The evidence as the record states it
Scandinavian Simvastatin Survival Study Group, 4S (The Lancet, 1994; PMID 7968073): 4,444 people with angina or a previous heart attack, simvastatin against placebo, median 5.4 years; deaths 182 (8%) against 256 (12%), relative risk 0.70; major coronary events 19% against 28%. Pravastatin, LIPID Study Group (New England Journal of Medicine, 1998; PMID 9841303): 9,014 people, pravastatin 40 mg, mean 6.1 years; overall mortality 11.0% against 14.1%. Heart Protection Study Collaborative Group (The Lancet, 2002; PMID 12114036): 20,536 high-risk adults aged 40 to 80, simvastatin 40 mg; deaths 12.9% against 14.7%; major vascular events 19.8% against 25.2%; annual excess myopathy about 0.01%. Baigent et al., Cholesterol Treatment Trialists' Collaboration (The Lancet, 2010; PMID 21067804): 26 trials, about 170,000 participants; all-cause death 10% lower per 1 mmol/L LDL reduction; no effect on cancer. Shepherd et al., WOSCOPS (New England Journal of Medicine, 1995; PMID 7566020): 6,595 men without a previous heart attack; definite coronary events 31% lower. Ridker et al., JUPITER (New England Journal of Medicine, 2008; PMID 18997196): 17,802 people with raised C-reactive protein; primary end point hazard ratio 0.56; more physician-reported diabetes. Yusuf et al., HOPE-3 (New England Journal of Medicine, 2016; PMID 27040132): 12,705 intermediate-risk people; hazard ratio 0.76; more cataract surgery and muscle symptoms. Taylor et al. (Cochrane Database of Systematic Reviews, 2013; PMID 23440795): 18 primary-prevention trials, 56,934 participants; all-cause death odds ratio 0.86. Mihaylova et al. (The Lancet, 2012; PMID 22607822): benefit per 1 mmol/L similar in low-risk people. Older people, Cholesterol Treatment Trialists' Collaboration (The Lancet, 2019; PMID 30712900): benefit in all age groups, less direct evidence over 75 without vascular disease. Shepherd et al., PROSPER (The Lancet, 2002; PMID 12457784): 5,804 people aged 70 to 82; primary end point hazard ratio 0.85; no effect on cognitive function or disability. Zoungas et al., STAREE (New England Journal of Medicine, 2026; PMID 42670961): 9,971 adults aged 70 or older without cardiovascular disease; cardiovascular events hazard ratio 0.70; disability-free survival hazard ratio 0.94, not significant. McGuinness et al. (Cochrane Database of Systematic Reviews, 2016; PMID 26727124): statins do not prevent cognitive decline or dementia. Harm sources, the first three from the Cholesterol Treatment Trialists' Collaboration. Muscle symptoms (The Lancet, 2022; PMID 36049498). Diabetes (The Lancet Diabetes and Endocrinology, 2024; PMID 38554713). Adverse effects listed on statin labels (The Lancet, 2026; PMID 41655587). Howard et al., SAMSON (Journal of the American College of Cardiology, 2021; PMID 34531021). Sattar et al. (The Lancet, 2010; PMID 20167359). Amarenco et al., SPARCL (New England Journal of Medicine, 2006; PMID 16899775), hemorrhagic stroke after a previous stroke. Trompet et al. (Journal of Neurology, 2010; PMID 19653027): the full PROSPER cognitive results, no difference between pravastatin and placebo. Joseph et al. (Journal of the American Geriatrics Society, 2023; PMID 37082807): the published design of PREVENTABLE, a trial of lipid lowering in older adults; it reports no results.
PMID 7968073 PMID 9841303 PMID 12114036 PMID 16214597 PMID 21067804 PMID 7566020 PMID 18997196 PMID 27040132 PMID 23440795 PMID 22607822 PMID 42670961 PMID 12457784 PMID 30712900 PMID 42580354 PMID 26727124 PMID 19653027 PMID 36049498 PMID 34531021 PMID 38554713 PMID 20167359 PMID 41655587 PMID 16899775 PMID 37082807 PMID 32616158
Evidence by specific use
Death and major cardiovascular events in people with coronary heart disease or other established vascular disease
Grade A
4S (PMID 7968073): 6-year survival 91.3% on simvastatin against 87.6% on placebo, 37 more people alive per 1,000 (arithmetic on the abstract's percentages). LIPID (PMID 9841303): 31 fewer deaths per 1,000 over a mean 6.1 years (arithmetic). Heart Protection Study (PMID 12114036): simvastatin 40 mg in 20,536 adults with coronary disease, other occlusive arterial disease or diabetes; deaths 12.9% against 14.7%; first major vascular event 19.8% against 25.2%, 54 fewer per 1,000 over about 5 years (arithmetic), an NNT of about 19, as on EBL's statin medication record. Baigent et al., Cholesterol Treatment Trialists' Collaboration (The Lancet, 2005; PMID 16214597): 48 fewer people with a major vascular event per 1,000 per 1 mmol/L lower LDL cholesterol in people with coronary heart disease. Replicated hard outcomes including death from any cause: A.
PMID 7968073 PMID 9841303 PMID 12114036 PMID 16214597 PMID 21067804
Heart attack, stroke and cardiovascular death in people without cardiovascular disease who are at raised risk
Grade A
Shepherd et al., WOSCOPS (1995; PMID 7566020): death from any cause 22 percent lower, at the edge of significance (95% CI 0 to 40 percent). Ridker et al., JUPITER (2008; PMID 18997196): rosuvastatin 20 mg in 17,802 people with LDL below 130 mg per deciliter and raised C-reactive protein; primary end point hazard ratio 0.56 and death from any cause 0.80 at a median 1.9 years, when the trial was stopped. Yusuf et al., HOPE-3 (2016; PMID 27040132): 11 fewer people per 1,000 with cardiovascular death, heart attack or stroke over a median 5.6 years (arithmetic on 3.7% against 4.8%). Taylor et al. (Cochrane Database of Systematic Reviews, 2013; PMID 23440795): 18 trials, 56,934 people with 10% or fewer having a history of cardiovascular disease; all-cause death odds ratio 0.86, combined cardiovascular events risk ratio 0.75; 14 of the 18 trials recruited people with raised lipids, diabetes, hypertension or microalbuminuria. Mihaylova et al. (The Lancet, 2012; PMID 22607822): in people whose 5-year risk was below 10%, about 11 fewer major vascular events per 1,000 over 5 years per 1 mmol/L lower LDL cholesterol. Replicated hard outcomes: A. The absolute benefit is smaller than after a heart attack because fewer events happen.
PMID 7566020 PMID 18997196 PMID 27040132 PMID 23440795 PMID 22607822
Major cardiovascular events in adults aged 70 and over without cardiovascular disease
Grade B
Zoungas et al., STAREE (New England Journal of Medicine, 2026; PMID 42670961): double-blind trial in Australian general practice, 9,971 community-dwelling adults aged 70 or older (mean 74.7) without cardiovascular disease, diabetes or dementia, atorvastatin 40 mg against placebo; after a median 5.9 years, cardiovascular death, heart attack, stroke or coronary revascularization 10.9 against 15.5 events per 1,000 person-years, hazard ratio 0.70; funded by the National Health and Medical Research Council and others. Shepherd et al., PROSPER (The Lancet, 2002; PMID 12457784): pravastatin 40 mg in 5,804 people aged 70 to 82 with a history of, or risk factors for, vascular disease; primary end point hazard ratio 0.85, coronary death and heart attack 0.81, stroke unaffected. Older people, Cholesterol Treatment Trialists' Collaboration (The Lancet, 2019; PMID 30712900): major vascular events fell in every age group, with less direct evidence of benefit in people older than 75 without vascular disease. Bonnet et al., SAGA/SITE (The Lancet Healthy Longevity, 2026; PMID 42580354): an open-label trial in 1,160 people aged 75 or older taking a statin for primary prevention found stopping it non-inferior to continuing for death over 3 years (7.2% against 7.9%). WHY NOT A: STAREE is the one trial in this population. PROSPER mixed people with and without vascular disease and is supporting evidence, not an independent repeat in people free of it. One well-designed trial with a meaningful effect, supported by PROSPER and the pooled data: B.
PMID 42670961 PMID 12457784 PMID 30712900 PMID 42580354
Disability-free survival (living without dementia or persistent physical disability) in adults aged 70 and over without cardiovascular disease
Grade D
STAREE is the one randomized trial of a statin that set a healthy-aging outcome as a primary end point. The same atorvastatin that cut cardiovascular events by 30 percent did not lengthen survival free of dementia and disability. Tested, no benefit: D on Route 2. PREVENTABLE, testing the same question in about 20,000 adults aged 75 or older, has not reported (trials in progress).
PMID 42670961
Preventing dementia and cognitive decline in older people
Grade D
McGuinness et al. (Cochrane Database of Systematic Reviews, 2016; PMID 26727124) found good evidence that statins given in late life to people at risk of vascular disease do not prevent cognitive decline or dementia. Trompet et al. (Journal of Neurology, 2010; PMID 19653027) reported the full PROSPER cognitive results: no difference. In STAREE (PMID 42670961) dementia was part of a composite that did not differ; the abstract does not report dementia alone. Tested, no benefit: D on Route 2. Population studies linking statin use to less dementia are not graded.
PMID 26727124 PMID 19653027 PMID 12457784 PMID 42670961
Why Grade A and not higher
Grade A requires a hard clinical endpoint or objectively measured functional outcome, independently replicated across at least two trials. Statins (simvastatin, pravastatin, atorvastatin, rosuvastatin) meets that standard based on the trials cited above. A downgrade to Grade B would follow if replication attempts produced null results, if the effect size proved substantially smaller in a broader population, or if the studied dose proved impractical to sustain.
What this grade covers and what it does not
Grade A by the replicated hard-outcome route, in two populations. In people with coronary heart disease, two independent placebo-controlled trials with different statins found fewer deaths from any cause: 4S with simvastatin (PMID 7968073) and LIPID with pravastatin (PMID 9841303), confirmed by the Heart Protection Study (PMID 12114036) and by pooled individual data from 26 trials (Baigent et al., 2010; PMID 21067804). In people without cardiovascular disease at raised risk, WOSCOPS (PMID 7566020), JUPITER (PMID 18997196) and HOPE-3 (PMID 27040132) each reduced heart attacks, strokes or cardiovascular deaths, and the Cochrane review found all-cause death lower (Taylor et al., 2013; PMID 23440795). In adults aged 70 and over without cardiovascular disease, one trial, STAREE, found 30 percent fewer cardiovascular events (PMID 42670961): B. The same trial found no longer survival free of dementia and disability (D, Route 2), and statins did not prevent dementia or cognitive decline (Cochrane 2016, PMID 26727124: D, Route 2). WHAT THIS GRADE DOES NOT COVER: no trial has tested statins for longevity in healthy, low-risk adults. The primary-prevention trials enrolled people with high cholesterol, raised C-reactive protein, intermediate risk or conditions such as diabetes and hypertension (14 of the 18 trials in the Cochrane review), and the only trial that set a healthy-aging outcome as a primary end point, STAREE in people aged 70 and over, found none. The A says statins prevent heart attacks, strokes and deaths in people at raised risk; it does not say they slow aging. The grade attaches to the statins and doses tested, not to red yeast rice, which EBL grades separately.
What would move this grade
A null result in a well-powered independent replication trial, or evidence that the effect does not hold at a practically sustainable dose, would prompt downgrade to Grade B.
How this was studied
Form: Statin tablets once daily against placebo or a less intensive statin: simvastatin, pravastatin, atorvastatin and rosuvastatin · Dose: Simvastatin 40 mg (Heart Protection Study); pravastatin 40 mg (WOSCOPS, LIPID, PROSPER); rosuvastatin 10 mg (HOPE-3) or 20 mg (JUPITER); atorvastatin 40 mg (STAREE); more intensive regimens were atorvastatin 40 to 80 mg or rosuvastatin 20 to 40 mg (PMID 36049498) · Population: People with coronary heart disease or other vascular disease (4S, LIPID, Heart Protection Study); people without cardiovascular disease with high cholesterol, raised C-reactive protein or intermediate risk (WOSCOPS, JUPITER, HOPE-3); adults aged 70 and over (PROSPER, STAREE) · Duration: Median 1.9 years (JUPITER, stopped early) to mean 6.1 years (LIPID) · What is sold differs: Generic statins are the same molecules the trials tested. The trials enrolled people with heart disease or raised cardiovascular risk, so the grade does not describe a healthy, low-risk adult taking a statin to slow aging.
How to track whether this is working
Prescription only; requires physician management. The trials measured LDL cholesterol, liver enzymes and muscle symptoms along the way, and counted clinical events.