Polypill Strategy Shows Promise for Heart Failure Treatment with Improved Outcomes and Adherence

Adults with heart failure with reduced ejection fraction who took a polypill combining medications prescribed for heart failure treatment showed improved heart function and symptoms, better quality of life, fewer hospitalizations and greater medication adherence than those taking the medications individually. The findings were presented at the American Heart Association's Scientific Sessions 2025 in New Orleans.

The study focused on addressing the concerning reality that only 15% of patients receive all guideline-recommended therapies at any dose for heart failure after hospitalization, according to study author Ambarish Pandey, M.D., M.S., FAHA, an associate professor of internal medicine at UT Southwestern Medical Center in Dallas. The research specifically targeted socially disadvantaged populations to demonstrate the positive impact of an easier-to-follow medication regimen requiring only one pill versus three pills daily.

The trial included 212 adults with HFrEF who were not receiving guideline-recommended treatment. Participants were randomly assigned to either the polypill regimen or enhanced standard care with individual pills. The polypill contained metoprolol succinate, spironolactone and empagliflozin, while all participants also took sacubitril-valsartan separately since it requires twice-daily dosing.

After six months, the results revealed significant advantages for the polypill group. Measures of left ventricular ejection fraction improved among all participants, with a 3% higher absolute LVEF among the polypill group compared to the enhanced standard care group. This improvement in heart function represents a meaningful clinical benefit for patients with heart failure.

The polypill approach demonstrated particularly strong results in reducing healthcare utilization, cutting heart failure-related hospitalizations and emergency room visits by 60%. This substantial reduction means patients in the polypill group were less than half as likely to need emergency care, potentially translating to both improved patient outcomes and reduced healthcare costs.

Quality of life measures showed notable improvement, with polypill patients reporting scores of 72 points versus 63 points for the standard care group on a 100-point scale using the Kansas City Cardiomyopathy Questionnaire-12. This approximate 9-point improvement indicates patients experienced less fatigue, fewer symptoms, and better overall well-being in their daily lives.

Perhaps most significantly, medication adherence showed dramatic improvement with the polypill strategy. Blood tests confirmed that 79% of polypill patients had detectable levels of the tested medications compared to only 54% in the enhanced standard care group. This represents more than 4-fold greater odds of taking all tested medications with the polypill approach.

The study population reflected significant social challenges, with 68% of participants having no health insurance or receiving county-sponsored health coverage, 42% reporting food insecurity, and 32% reporting housing instability. The diverse participant pool included 54% who self-identified as Black and 33% who were Hispanic, with a median age of 54 years and 22% female representation.

Heart failure affects approximately 6.7 million adults in the U.S., with cases expected to increase to more than 8 million by 2030 according to American Heart Association statistics available at https://www.heart.org. Heart failure with reduced ejection fraction means the individual's ejection fraction is equal to or less than 40%, indicating the percentage of blood that leaves the left ventricle with each heartbeat.

The study authors plan additional research to evaluate broader implementation of the polypill approach in heart failure treatment. The findings suggest that simplifying medication regimens through combination pills could address critical barriers to optimal heart failure management, particularly for vulnerable populations who face multiple social determinants of health challenges.