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

Patients with heart failure and reduced ejection fraction who took a single combination pill containing three heart failure medications showed significant improvements in heart function, fewer hospitalizations, and better quality of life compared to those taking the same medications as separate pills, according to research presented at the American Heart Association's Scientific Sessions 2025. The study marks the first evaluation of a polypill strategy specifically for heart failure with reduced ejection fraction (HFrEF), focusing on simplifying treatment and improving medication adherence in a population where only 15% of patients receive all guideline-recommended therapies after hospitalization.

The trial involved 212 adults with HFrEF who were not receiving guideline-recommended treatment, with participants randomly assigned to either the polypill regimen or enhanced standard care using separate medications. The polypill contained metoprolol succinate, spironolactone, and empagliflozin, while both groups also took sacubitril-valsartan separately since it requires twice-daily dosing. After six months, researchers observed a 3.4% higher absolute left ventricular ejection fraction in the polypill group, indicating improved heart pumping function. More dramatically, the polypill reduced heart failure-related hospitalizations and emergency room visits by 60%, meaning patients taking the combination pill were less than half as likely to require emergency care.

Quality of life measures showed substantial improvement, with polypill patients scoring approximately 9 points higher on the 100-point Kansas City Cardiomyopathy Questionnaire-12, indicating less fatigue, fewer symptoms, and better overall well-being. Medication adherence proved significantly better in the polypill group, with blood tests confirming detectable levels of the tested medications in 79% of polypill patients compared to only 54% in the standard care group. This represents more than 4-fold greater odds of patients taking all tested medications when using the polypill approach.

Study author Ambarish Pandey, M.D., M.S., FAHA, emphasized the importance of these findings for addressing treatment gaps, particularly in socially disadvantaged populations. The study population reflected this focus, with 68% of participants having no health insurance or receiving county-sponsored health coverage, 42% reporting food insecurity, and 32% reporting housing instability. Participants were recruited from Parkland Health and Hospital System, Dallas County's safety-net health care system, along with UT Southwestern Medical Center and William F. Clements University Hospital.

The implications of these findings are significant given the rising prevalence of heart failure in the United States. According to American Heart Association data available here, approximately 6.7 million adults currently live with heart failure, with projections expecting this to increase to more than 8 million by 2030. Heart failure with reduced ejection fraction specifically indicates that the heart's left ventricle pumps 40% or less of its blood volume with each heartbeat. The study's participants began with an average left ventricular ejection fraction of 26%, well below the HFrEF threshold.

Researchers used comprehensive assessment methods including cardiac magnetic resonance imaging for heart function measurements, NT-proBNP blood testing to measure heart stress hormones, and multiple adherence measurement tools. The research team plans additional studies to evaluate broader implementation of the polypill approach in heart failure management. While these findings are promising, the study authors note that the research is preliminary until published as a full manuscript in a peer-reviewed scientific journal, as is standard for abstracts presented at scientific meetings.