Polypill Strategy Shows Promise for Heart Failure Patients 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 research presented at the American Heart Association's Scientific Sessions 2025 represents the first study to evaluate a polypill strategy in people with HFrEF, focused on improving medication adherence and simplifying treatment.

Study author Ambarish Pandey, M.D., M.S., FAHA, noted that despite important treatment advances for heart failure patients, use of these treatments remains disappointingly low, with only 15% of patients receiving all guideline-recommended therapies at any dose for heart failure after hospitalization. The trial specifically focused on socially disadvantaged populations to demonstrate the positive impact of an easier-to-follow medication regimen of only one pill versus three pills daily, finding significant improvements even after six months.

The trial included 212 adults with HFrEF who were not receiving guideline-recommended treatment. Participants were randomly assigned to either the polypill regimen, which included metoprolol succinate, spironolactone and empagliflozin, or enhanced standard care taking guideline-recommended medications as individual pills. All participants also took sacubitril-valsartan, which is dosed twice-daily and not well suited for a once-daily polypill.

After six months, the study revealed compelling results. Measures of left ventricular ejection fraction improved among all participants, with a 3% higher absolute LVEF among the polypill group versus the enhanced standard care group. The polypill reduced heart failure-related hospitalizations and emergency room visits by 60%, meaning patients in the polypill group were less than half as likely to need emergency care. Patients in the polypill group also reported higher quality of life scores than those in the enhanced standard care group, experiencing less fatigue, fewer symptoms, and better overall well-being.

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, with more than 4-fold greater odds of taking all tested medications with the polypill. The study enrolled participants from Parkland Health and Hospital System, Dallas County's safety-net health care system, UT Southwestern Medical Center and the William F. Clements University Hospital, all in Dallas. Participants represented a diverse population with 54% self-identifying as Black, 33% Hispanic, and 68% having no health insurance or receiving county-sponsored health coverage.

According to the American Heart Association, heart failure is a serious, long-term condition affecting about 6.7 million adults in the U.S., with cases expected to increase to more than 8 million by 2030. 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, potentially offering a simplified treatment strategy that could significantly impact patient outcomes and healthcare utilization. Additional information about heart failure management can be found at https://www.heart.org/en/health-topics/heart-failure and the full guidelines are available at https://www.heart.org/en/guidelines.