Benefits of the Polypill on Medication Adherence in the Primary and Secondary Prevention of Cardiovascular Disease: A Systematic Review

Background: Higher medication adherence reduces the risk of new cardiovascular events. However, there are individual and health system barriers that lead to lower adherence. The polypill has demonstrated benefits in cardiovascular morbidity and mortality mainly driven by an increase in adherence. We aim to evaluate the impact of the polypill on adherence to cardiovascular medication, its efficacy and safety in cardiovascular disease (CVD) prevention. Methods: A systematic review following PRISMA guidelines was conducted. Databases were searched from January 2003 to December 2022. We included randomized, pragmatic, or real-world clinical trials and observational studies. The primary outcome was medication adherence, secondary outcomes were efficacy in cardiovascular disease in primary and secondary prevention and safety. Results: From the 490 publications screened, 13 met the inclusion criteria and were incorporated into a comparative table Of those included, 70% were randomized controlled trials (RCTs) and 53.8% focused on secondary prevention. Most of the studies received a high and moderate quality rating. Self-report, pill counting and, the Morisky scale were the most frequent methods to evaluate adherence (84.6%). Compared with standard medication, the polypill improved overall medication adherence by 13%, with percen-tages ranging from 7.6% to 34.9%. Moreover, a potential benefit was also observed in reducing Major Adverse Cardiovascular Events (MACE), particularly in secondary prevention studies, with hazard ratios ranged between 0.43 to 0.76. Compared to standard care, the profile of side effects was similar. Conclusion: The polypill is an effective, safe, and practical strategy to improve adherence in people at risk of CVD. Although there is a demonstrated benefit in reducing MACE, predominantly in secondary prevention, there are still gaps in its efficacy in primary prevention and reducing total mortality. Therefore, the importance of obtaining long-term results of the polypill effect and how this strategy can be implemented in real practice.