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Polypills With and Without Aspirin for Primary Prevention of CVD
Quick Takes
- Fixed-dose combinations of ≥2 blood pressure-lowering medications with a statin are associated with reductions in CVD events in primary prevention populations.
- The inclusion of aspirin in the polypill is associated with larger reductions in CVD events than polypill medication without aspirin.
- Lower risk for MI, stroke, and CV death was associated with polypills compared to control.
- Combinations of fixed-dose pills may provide cost-effective prevention management for those at higher atherosclerotic CVD risk.
Study Questions:
Is the addition of aspirin in fixed-dose combination treatment (i.e., polypills) associated with reductions for cardiovascular disease (CVD) outcomes?
Methods:
The investigators conducted a meta-analysis including large randomized controlled trials (RCTs), which examined the use of a polypill. Each study enrolled ≥1,000 participants and ≥2 years of follow-up. The included RCTs compared a fixed-dose combination strategy of ≥2 blood pressure-lowering agents plus a statin (with or without aspirin) compared with a control strategy (placebo or usual care). Participants were considered a primary CVD prevention population. The primary outcome of interest was a composite CVD outcome including CV death, myocardial infarction (MI), stroke, or arterial revascularization. Additional outcomes included individual CV outcomes and death from any cause. Outcomes were also evaluated in groups stratified by the inclusion of aspirin in the fixed-dose treatment strategy.
Results:
Three RCTs were included in the present analysis (TIPS-3, HOPE-3, and PolyIran) for a total of 18,162 participants. The mean age of the study population was 63 years, and 49.8% were women (n = 9,038). The estimated 10-year CVD risk for the cohort was 17.7% calculated using the Framingham Risk Score. Over a median follow-up of 5 years, the primary outcome occurred in 276 (3.0%) participants who received the fixed-dose combination polypill, compared to 445 (4.9%) in the control group for a hazard ratio (HR) of 0.62 (95% confidence interval [CI], 0.53-0.73). For MI, reduced risk was observed for the polypill group (HR, 0.52; 95% CI, 0.38-0.70). Reductions for stroke (HR, 0.59; 95% CI, 0.45-0.78), revascularization (HR, 0.54; 95% CI, 0.36-0.80), and CV death (HR, 0.65; 95% CI, 0.52-0.81) were also observed for the polypill group compared to the control group.
Significant reductions in the primary outcome and its components were observed in the analyses of fixed-dose combination strategies with and without aspirin, with greater reductions for strategies including aspirin. Treatment effects were similar at different lipid and blood pressure levels and in the presence or absence of diabetes, smoking, or obesity. Gastrointestinal bleeding was uncommon but slightly more frequent in the fixed-dose combination strategy with the aspirin group versus control (0.4% vs. 0.2%, p = 0.15). The frequencies of hemorrhagic stroke (0.2% vs. 0.3%), fatal bleeding (<0.1% vs. 0.1%), and peptic ulcer disease (0.7% vs. 0.8%) were low and did not differ significantly between groups. Dizziness was more common with fixed-dose combination treatment (11.7% vs. 9.2%, p < 0.0001).
Conclusions:
The investigators concluded that fixed-dose combination treatment strategies substantially reduce CVD, MI, stroke, revascularization, and CV death in primary CVD prevention. These benefits are consistent irrespective of cardiometabolic risk factors.
Perspective:
These data support the development and evaluation of fixed-dose combination pills for the primary prevention of CVD among adults at risk for CVD. It should be noted that the risk for CVD among the included participants was not low; however, the best cut-point in terms of atherosclerotic CVD risk for prescription of a polypill strategy remains to be determined.
Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Vascular Medicine, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Smoking
Keywords: Aspirin, Atherosclerosis, Blood Pressure, Cardiovascular Diseases, Diabetes Mellitus, Gastrointestinal Hemorrhage, Hemorrhagic Stroke, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipids, Metabolic Syndrome, Myocardial Infarction, Peptic Ulcer, Prescriptions, Primary Prevention, Risk Factors, Smoking, Stroke, Vascular Diseases
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