Statins for Prevention of Cardiovascular Disease in Adults
Authors: Roger Chou, Tracy Dana, Ian Blazina, Monica Daeges, Thomas L. Jeanne
Journal: JAMA (2016)

<h3>Importance</h3> Cardiovascular disease (CVD), the leading cause of mortality and morbidity in the United States, may be potentially preventable with statin therapy. <h3>Objective</h3> To systematically review benefits and harms of statins for prevention of CVD to inform the US Preventive Services Task Force. <h3>Data Sources</h3> Ovid MEDLINE (from 1946), Cochrane Central Register of Controlled Trials (from 1991), and Cochrane Database of Systematic Reviews (from 2005) to June 2016. <h3>Study Selection</h3> Randomized clinical trials of statins vs placebo, fixed-dose vs titrated statins, and higher- vs lower-intensity statins in adults without prior cardiovascular events. <h3>Data Extraction and Synthesis</h3> One investigator abstracted data, a second checked data for accuracy, and 2 investigators independently assessed study quality using predefined criteria. Data were pooled using random-effects meta-analysis. <h3>Main Outcomes and Measures</h3> All-cause mortality, CVD-related morbidity or mortality, and harms. <h3>Results</h3> Nineteen trials (n = 71 344 participants [range, 95-17 802]; mean age, 51-66 years) compared statins vs 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];<i>I</i><sup>2</sup> = 0%; absolute risk difference [ARD], −0.40% [95% CI, −0.64% to −0.17%]), cardiovascular mortality (RR, 0.82 [95% CI, 0.71 to 0.94];<i>I</i><sup>2</sup> = 0%; ARD, −0.20% [95% CI, −0.35% to −0.05%];<i>I</i><sup>2</sup> = 11%), stroke (RR, 0.71 [95% CI, 0.62 to 0.82];<i>I</i><sup>2</sup> = 0; ARD, −0.38% [95% CI, −0.53% to −0.23%]), myocardial infarction (RR, 0.64 [95% CI, 0.57 to 0.71];<i>I</i><sup>2</sup> = 0%; ARD, −0.81% [95% CI, −1.19 to −0.43%]), and composite cardiovascular outcomes (RR, 0.70 [95% CI, 0.63 to 0.78];<i>I</i><sup>2</sup> = 36%; ARD, −1.39% [95% CI, −1.79 to −0.99%]). Relative benefits appeared consistent in demographic and clinical subgroups, including populations without marked hyperlipidemia (total cholesterol level &lt;200 mg/dL); absolute benefits were higher in subgroups at higher baseline risk. Statins were not associated with increased risk of serious adverse events (RR, 0.99 [95% CI, 0.94 to 1.04]), myalgias (RR, 0.96 [95% CI, 0.79 to 1.16]), or liver-related harms (RR, 1.10 [95% CI, 0.90 to 1.35]). In pooled analysis, statins were not associated with increased risk of diabetes (RR, 1.05 [95% CI, 0.91 to 1.20]), although statistical heterogeneity was present (<i>I</i><sup>2</sup> = 52%), and 1 trial found high-intensity statins associated with increased risk (RR, 1.25 [95% CI, 1.05 to 1.49]). No trial directly compared titrated vs fixed-dose statins, and there were no clear differences based on statin intensity. <h3>Conclusions and Relevance</h3> In adults at increased CVD risk but without prior CVD events, statin therapy was associated with reduced risk of all-cause and cardiovascular mortality and CVD events, with greater absolute benefits in patients at greater baseline risk.