Chou · JAMA 2022 · Systematic review and meta-analysis · n=26 studies (95,768 RCT participants; 417,523 observational participants)

Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Cited 283 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of randomized controlled trials

PubMed 35997724 · doi:10.1001/jama.2022.12138 · record verified 2026-08-29

What was done

Systematic review and meta-analysis updating the 2016 US Preventive Services Task Force evidence report on statins for the primary prevention of cardiovascular disease (CVD) in adults without prior cardiovascular events. Databases (Ovid MEDLINE, Cochrane Central, and Cochrane Database of Systematic Reviews) were searched through November 2021 with surveillance through May 2022. The review synthesized 22 randomized trials (N = 90,624; follow-up 6 months to 6 years) comparing statins with placebo or no statin, 1 trial (n = 5,144) comparing statin intensities, and 3 cohort studies (n = 417,523) reporting harms.

What was found

Statins significantly reduced all-cause mortality (RR 0.92 [95% CI, 0.87 to 0.98]; ARD -0.35% [95% CI, -0.57% to -0.14%]), stroke (RR 0.78 [95% CI, 0.68 to 0.90]; ARD -0.39% [95% CI, -0.54% to -0.25%]), myocardial infarction (RR 0.67 [95% CI, 0.60 to 0.75]; ARD -0.85% [95% CI, -1.22% to -0.47%]), and composite cardiovascular outcomes (RR 0.72 [95% CI, 0.64 to 0.81]; ARD -1.28% [95% CI, -1.61% to -0.95%]). Cardiovascular mortality reduction was not statistically significant (RR 0.91 [95% CI, 0.81 to 1.02]; ARD -0.13%). Statins were not significantly associated with serious adverse events (RR 0.97 [95% CI, 0.93 to 1.01]), myalgias (RR 0.98 [95% CI, 0.86 to 1.11]), elevated alanine aminotransferase (RR 0.94 [95% CI, 0.78 to 1.13]), or overall incident diabetes (RR 1.04 [95% CI, 0.92 to 1.19]), though one trial reported increased diabetes risk with high-intensity statin therapy (RR 1.25 [95% CI, 1.05 to 1.49]).

Why it matters

This review reinforces that statin therapy delivers consistent relative reductions in fatal and nonfatal cardiovascular events in primary prevention populations without excess risk of myalgias or serious adverse events.

Limits

Trial data for adults older than 75 years were sparse. Duration of trial follow-up was limited to 6 years, which is shorter than real-world decades-long preventive use. Data directly comparing different statin intensities were restricted to a single trial.

Cited by