Drugs for Primary Prevention of Atherosclerotic Cardiovascular Disease

Abstract

Importance The Million Hearts initiative emphasizes the “ABCS” - aspirin, blood pressure control, cholesterol management, and smoking cessation. Evidence for the effects of drugs used to achieve the ABCS has not been comprehensively synthesized in primary atherosclerotic cardiovascular disease (ASCVD) prevention. Objective To compare the efficacy and safety of aspirin, blood pressure-lowering therapy, statin, and tobacco cessation drugs on fatal and non-fatal ASCVD outcomes in primary ASCVD prevention. Evidence Review 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 formethodologic 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. Findings 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. Conclusions and Relevance This overview demonstrates high quality evidence to support aspirin, blood pressure-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 clinician-patient discussions in primary ASCVD prevention.

Estimating Longitudinal Risks and Benefits From Cardiovascular Preventive Therapies Among Medicare Patients

“…6 Briefly, we used standardized methods outlined in the Cochrane Handbook of Systematic Reviews 54 (www.handbook.cochrane.org) for the performance of an overview of systematic reviews for each of the following interventions for primary ASCVD prevention: aspirin, blood pressure–lowering therapy, statins, and pharmacologic tobacco cessation strategies. Of note, we focused specifically on statins for cholesterol management because of the extensive evidence base and endorsement of statins by numerous guidelines as the primary means for management of LDL-cholesterol to reduce ASCVD risk.…”

“…6 We searched for trials that had assessed the effects on ASCVD risk of concomitant drug treatment (compared with single component treatment alone) using any one of the following combinations: aspirin + blood pressure–lowering therapy; aspirin + statin therapy; blood pressure–lowering + statin therapy; or aspirin + blood pressure–lowering therapy + statin therapy.…”

“…Effective strategies exist for the primary prevention of ASCVD, 6 but they are currently underutilized or not applied to the appropriate spectrum of patients, with clear undertreatment of higher-risk patient groups for whom efficacy has been demonstrated. 1,7,8 Aspirin prevents ASCVD in certain groups, but its use must be weighed against the risk for major bleeding.…”

Statins alone or polypill for primary prevention of cardiovascular diseases

“…Many of these deaths may be prevented with use of approved medications. Guidelines strongly recommend the use of medicines including aspirin, statins, beta blockers, and angiotensin-converting enzyme (ACE) inhibitors or angiotensin-II receptors blockers (ARBs) for prevention of CVD risk factors including hypertension, dyslipidemia and thrombosis [3]. Nowadays fixed-dose combination therapy is recommended.…”

“…Moreover, Karmali et al (2016) searched the systematic reviews which evaluated the effect of aspirin, blood pressure-lowering therapy, or statins on cardiovascular events in individuals without prevalent CVD. They showed that aspirin, statins and BP-lowering therapy individually reduced the risk for CVD compared with placebo by 10%, 25% and 16% respectively [3]. …”