Polypill and its association with cardiovascular morbidity and mortality: meta-analysis from randomized controlled trials

Abstract

Background: Polypill or fixed dose combination pill (containing antihypertensive and cholesterol lowering agents) has shown, in multiple studies, to increase adherence and improve blood pressure and cholesterol measurements in at risk underprivileged populations. However, its long term effect on mortality, cardiovascular and cerebrovascular outcomes in high risk groups is not well-established. Objective: To assess mortality, cardiovascular and cerebrovascular outcomes in higher risk patients using polypill containing fixed dose of Aspirin, antihypertensive drugs and Statin compared to standard care or placebo. Methods: We queried MEDLINE, COCHRANE, and EMBASE databases for randomized controlled trials (RCTs) comparing polypill containing Aspirin, Statin and at least 2 antihypertensive medications, to standard care or placebo in patients with increased risk of cardiovascular diseases. We looked for trials including data about mortality, coronary and cerebrovascular events. We excluded trials that did not include outcomes of interest. 5 RCTs matching our criteria were included in our meta-analysis; UMPIRE 2013, IMPACT 2014, Kanyini GAP 2015, PolyIran 2019, and TIPS-3 2021. Results: 12828 patients (6419 in polypill vs 6409 in standard care/placebo groups) with known all-cause mortality, coronary events and cerebrovascular events outcomes were analyzed from 5 RCTs. For cardiovascular mortality outcome, 12205 patients (6108 in polypill vs 6097 in standard care/placebo groups) were analyzed from 4 RCTs since 1 RCT lacked data about cardiovascular mortality outcome. There was no difference between both groups in all four outcomes. Risk ratio of all-cause morality and cardiovascular mortality in polypill group was 0.89 [95% CI 0.76-1.03, P=0.11, I2=0%] and 0.77 [95% CI 0.48-1.26, P=0.31, I2=59%] respectively (Figure 1). Risk ratio of coronary events in polypill group was 0.88 [95% CI 0.64-1.20, P=0.41, I2=40%]. Relative risk of cerebrovascular events was 0.73 [95% CI 0.36-1.48, P=0.38, I2=63%] (Figure 2). Conclusion: Polypill, despite being a practical solution to non-adherence in at risk underprivileged groups, does not improve mortality or major cardiovascular or cerebrovascular outcomes compared to standard care or placebo. Further efforts need to be made towards aggressive preventative measures and encouraging adherence to medications in groups at risk. (Figure Presented).