Polypill Therapy and Risk of Adverse Cardiovascular Events and Mortality

At this year’s AHA Scientific Sessions, we presented findings from our systematic review and meta-analysis evaluating the impact of polypills – single pill combinations of common preventive cardiac therapies – on cardiovascular outcomes and risk factors. Globally today, cardiovascular disease is on the rise, with optimal risk reduction therapies not reaching most at-risk adults due to failures to prescribe evidence-based treatments and patient barriers to adherence to recommended therapies. Although polypills have long been theorized to have the potential to dramatically improve cardiovascular risk reduction in low- and middle-income countries due to their ease of use for providers and patients alike, data supporting this approach have been sparse until recently.

Therefore, we performed a systematic search to identify randomized controlled trials that examined the associations between polypill therapy and cardiovascular outcomes and all-cause mortality. We identified eight high-quality randomized control trials published between 2013 and 2020, which collectively enrolled 25,584 participants, had a median follow up of about three years, and reported on major adverse cardiovascular events (such as cardiovascular death, acute coronary syndromes, stroke, heart failure, myocardial infarction, cardiac arrest, arterial revascularization, and angina). Included trials represented both primary and secondary prevention applications of the polypill and were primarily set in low- and middle-income countries, though seven of the trials included at least one high-income country. We additionally evaluated the effect of the polypill strategy on clinically relevant secondary endpoints, including the risk of all-cause mortality, changes in blood pressure and cholesterol, adverse therapy effects, and drug adherence and discontinuation rates.

In our study-level meta-analysis, we found that use of the polypill was associated with a 15% reduction in the incidence of cardiovascular events overall, though this result was not significant. The impact of the polypill was most apparent among trials that implemented a primary prevention application, enrolling patients without preexisting cardiovascular disease, where we observed a significant 30% reduction in the risk of cardiovascular events. In contrast, no favorable effect was observed among trials evaluating patients with preexisting cardiovascular disease. The polypill strategy in the overall cohort did, however, demonstrate additional benefits with secondary outcomes, including a significant reduction in all-cause mortality, blood pressure, and drug discontinuation, with a corresponding increase in adherence to therapy among individuals receiving the single pill.

Together, this meta-analysis of RCTs demonstrates that a polypill strategy is associated with substantial overall reductions in cardiovascular events and intermediate cardiovascular endpoints, particularly when applied for primary prevention as a population-level strategy. Such an approach, if employed effectively, may have substantial implications for the accessibility of cardiac preventive therapies around the world.