Background: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in the United States but is potentially preventable with statin therapy. The U.S. Preventive Services (USPSTF) commissioned this review to inform the development of new recommendations on use of statin therapy for prevention of CVD in adults.
Purpose: To evaluate benefits and harms of statin therapy for prevention of CVD in adults without prior cardiovascular events.
Data Sources: We searched the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and MEDLINE to June 2016 and manually reviewed reference lists.
Study Selection: Randomized, controlled trials on the benefits and harms of statin therapy versus placebo or no statin in adults without prior cardiovascular events.
Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF.
Data Synthesis (Results): Nineteen trials with followup from 6 months to 6 years compared statin therapy versus placebo or no statin. Statin therapy was associated with decreased risk of all-cause mortality (risk ratio [RR], 0.86 [95% CI, 0.80 to 0.93]; absolute risk difference [ARD], -0.40%; number needed to treat [NNT], 250), cardiovascular mortality (RR, 0.82 [95% CI, 0.71 to 0.94]; ARD, -0.20%; NNT, 500), stroke (RR, 0.71 [95% CI, 0.62 to 0.82]; ARD, -0.38%; NNT, 263), myocardial infarction (RR, 0.64 [95% CI, 0.57 to 0.71]; ARD, -0.81%; NNT, 123), and composite cardiovascular outcomes (RR, 0.70 [95% CI, 0.63 to 0.78]; ARD, -1.39%; NNT, 72). Relative benefits appeared to be consistent in subgroups defined by demographic and clinical characteristics, including populations with cardiovascular risk factors without marked hyperlipidemia. Statin therapy was not associated with significantly increased risk of serious adverse events (RR, 0.99 [95% CI, 0.94 to 1.04]), myalgia (RR, 0.96 [95% CI, 0.79 to 1.16]), or liver-related harms (RR, 1.10 [95% CI, 0.90 to 1.35]). Statins were not associated with increased risk of diabetes (RR, 1.05 [95% CI, 0.91 to 1.20]), though statistical heterogeneity was present (I2=52%), and one trial found that high-intensity statins were associated with increased risk (RR, 1.25 [95% CI, 1.05 to 1.49]). No trial directly compared titrated versus fixed-dose statin therapy. Based on an analysis of individual patient data from randomized trials, greater reductions in low-density lipoprotein cholesterol levels with statin therapy are associated with reduced risk of CVD events, which may provide some indirect evidence that higher-intensity therapy may be associated with better clinical outcomes than lower-intensity therapy.
Limitations: Restricted to English language, statistical heterogeneity in some pooled analyses, and limited formal assessment for publication bias.
Conclusions: In adults at increased CVD risk but without prior CVD events, statin therapy is associated with reduced risk of all-cause and cardiovascular mortality and CVD events. Benefits appear to be present across diverse demographic and clinical subgroups, with greater absolute benefits in patients at higher baseline risk, and do not appear to be restricted to patients with marked hyperlipidemia.