Drugs for Primary Prevention of Atherosclerotic Cardiovascular Disease
Authors: Kunal N. Karmali, Donald M. Lloyd-Jones, Mark A. Berendsen, David C. Goff, Darshak M. Sanghavi, Nina C. Brown, Liliya Korenovska, Mark D. Huffman
Journal: JAMA Cardiology (2016)

<h3>Importance</h3> The Million Hearts initiative emphasizes ABCS (<i>a</i>spirin for high-risk patients,<i>b</i>lood pressure [BP] control,<i>c</i>holesterol level management, and<i>s</i>moking cessation). Evidence of the effects of drugs used to achieve ABCS has not been synthesized comprehensively in the prevention of primary atherosclerotic cardiovascular disease (ASCVD). <h3>Objective</h3> To compare the efficacy and safety of aspirin, BP-lowering therapy, statins, and tobacco cessation drugs for fatal and nonfatal ASCVD outcomes in primary ASCVD prevention. <h3>Evidence Review</h3> Structured search of the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA), MEDLINE, EMBASE, and PROSPERO International Prospective Systematic Review Trial Register to identify systematic reviews published from January 1, 2005, to June 17, 2015, that reported the effect of aspirin, BP-lowering therapy, statin, or tobacco cessation drugs on ASCVD events in individuals without prevalent ASCVD. Additional studies were identified by searching the reference lists of included systematic reviews, meta-analyses, and health technology assessment reports. Reviews were selected according to predefined criteria and appraised for methodologic quality using the Assessment of Multiple Systematic Reviews (AMSTAR) tool (range, 0-11). Studies were independently reviewed for key participant and intervention characteristics. Outcomes that were meta-analyzed in each included review were extracted. Qualitative synthesis was performed, and data were analyzed from July 2 to August 13, 2015. <h3>Findings</h3> From a total of 1967 reports, 35 systematic reviews of randomized clinical trials were identified, including 15 reviews of aspirin, 4 reviews of BP-lowering therapy, 12 reviews of statins, and 4 reviews of tobacco cessation drugs. Methodologic quality varied, but 30 reviews had AMSTAR ratings of 5 or higher. Compared with placebo, aspirin (relative risk [RR], 0.90; 95% CI, 0.85-0.96) and statins (RR, 0.75; 95% CI, 0.70-0.81) reduced the risk for ASCVD. Compared with placebo, BP-lowering therapy reduced the risk for coronary heart disease (RR, 0.84; 95% CI, 0.79-0.90) and stroke (RR, 0.64; 95% CI, 0.56-0.73). Tobacco cessation drugs increased the odds of continued abstinence at 6 months (odds ratio range, 1.82 [95% CI, 1.60-2.06] to 2.88 [95% CI, 2.40-3.47]), but the direct effects on ASCVD were poorly reported. Aspirin increased the risk for major bleeding (RR, 1.54; 95% CI, 1.30-1.82), and statins did not increase overall risk for adverse effects (RR, 1.00; 95% CI, 0.97-1.03). Adverse effects of BP-lowering therapy and tobacco cessation drugs were poorly reported. <h3>Conclusions and Relevance</h3> This overview demonstrates high-quality evidence to support aspirin, BP-lowering therapy, and statins for primary ASCVD prevention and tobacco cessation drugs for smoking cessation. Treatment effects of each drug can be used to enrich discussions between health care professionals and patients in primary ASCVD prevention.