Statins (simvastatin, pravastatin, atorvastatin, rosuvastatin)

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 Number needed to treat: how many people must receive a treatment for one of them to benefit, compared with the control group. 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.

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 How often an event happened in the treated group compared with the control group over the same period. A ratio of 0.80 means 20 percent fewer events. 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 A review that searches for every study on a question using a method set in advance, then assesses them together., 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.

Zoungas et al., STAREE (New England Journal of Medicine, 2026; PMID 42670961): double-blind Neither the participants nor the people assessing them know who received the real treatment until the trial ends. 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 Everyone in the trial knows which treatment they are receiving, so expectations can shape the results, especially for symptoms people report themselves. 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.

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 Human randomized trials have been run and did not show benefit on the stated outcome. One of the two routes to the lowest letter on EBL's scale.. PREVENTABLE, testing the same question in about 20,000 adults aged 75 or older, has not reported (trials in progress).

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.