Combination pill for heart failure improved heart function, symptoms and quality of life

Research Highlights:

• Among patients with heart failure and reduced ejection fraction (HFrEF), those taking a "polypill" combination of three medications typically prescribed for heart failure, once daily for six months, had improved heart function and symptoms, better quality of life, fewer hospitalizations and greater medication adherence in comparison to those who took the same medications as separate pills.
• This is the first study to evaluate a polypill strategy in people with HFrEF, focused on improving medication adherence and simplifying treatment.
• The people who took the polypill, when compared to the those who took the medications in separate pills, had increased heart function (3.4% higher absolute left ventricular ejection fraction), reduced rates of hospitalization or emergency care for heart failure by more than half, and reported a higher quality of life.
• Note: The study featured in this news release is a research abstract. Abstracts presented at American Heart Association's scientific meetings are not peer-reviewed, and the findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal.

Embargoed until 9:45 a.m. CT/10:45 a.m. ET, Monday, Nov. 10, 2025

NEW ORLEANS, Nov. 10, 2025 - Adults with heart failure with reduced ejection fraction (HFrEF) who took a "polypill" combining medications prescribed for the treatment of heart failure, had improved heart function and symptoms, better quality of life, fewer hospitalizations and greater medication adherence than those taking the medications individually, according to a late-breaking science presentation today at the American Heart Association's Scientific Sessions 2025. The meeting, Nov. 7-10, in New Orleans, is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science.

"In recent decades, there have been important, effective treatment advances for patients with heart failure, however, 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," said study author Ambarish Pandey, M.D., M.S., FAHA, an associate professor of internal medicine in the division of cardiology and geriatrics at UT Southwestern Medical Center in Dallas and medical director of the center's heart failure with preserved ejection fraction program. "In our study, we focused on socially disadvantaged populations to demonstrate the positive impact of an easier-to-follow medication regimen of only one pill vs. three pills daily, and we found significant improvements even after six months. Our findings provide the first evidence that a polypill approach could be effective for our patients with heart failure."

The trial included 212 adults with HFrEF who were not receiving guideline-recommended treatment. Participants were randomly assigned to one of two groups: 108 participants were prescribed the polypill regimen, which included metoprolol succinate (a beta-blocker), spironolactone (a mineralocorticoid receptor antagonist) and empagliflozin (a SGLT2 inhibitor). The second group of 104 adults were assigned to enhanced standard care, taking guideline-recommended medications as individual pills. Everyone also took an angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril-valsartan, which is dosed twice-daily and not well suited for a once-daily polypill.

After six months, the study found:

• Measures of left ventricular ejection fraction (LVEF) improved among all participants, with a 3% higher absolute LVEF among the polypill group vs. 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 reported higher quality of life scores than those in the enhanced standard care group (72 points vs. 63 points, on a 100-point scale). This approximate 9-point improvement means patients experienced less fatigue, fewer symptoms, and better overall well-being.
• Blood tests confirmed that 79% of polypill patients had detectable levels of the tested medications (metoprolol and/or spironolactone), 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 group plans more research on how best to address heart failure in specific groups.

"Moving forward, we are planning additional studies to evaluate broader implementation of the polypill approach in heart failure," Pandey said.

Study details, background or design:

• 212 adults with HFrEF (left ventricular ejection fraction of equal to or less than 40%) were enrolled. Participants were a median age of 54 years old; 22% were female; 54% self-identified as Black, and 33% were Hispanic; 68% of participants had no health insurance or were receiving county-sponsored health coverage; 42% reported food insecurity; and 32% reported housing instability.
• Participants were recruited 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.
• The trial enrolled participants over approximately 3.5 years, and enrollment closed in May 2025.
• Nearly half of participants were prescribed all four medication types at enrollment, however, 73% had moderate-to-low medication adherence.
• When the study started, the participants' average left ventricular ejection fraction was 26%.
• Various health measures and data were collected at time of enrollment, one month, three months and the final patient data was collected at six months.
• All participants had their heart's left ventricular ejection fraction measured by cardiac magnetic resonance imaging (MRI) at enrollment and at the six-month follow-up.
• Blood samples were collected at all study visits to measure levels of a protein hormone that is released by the heart in response to stress, such as heart failure. This is referred to as NT-proBNP testing.
• Health-related quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire-12, a standard patient questionnaire.
• Medication adherence was assessed through multiple methods including the Morisky Medication Adherence Questionnaire-8, and therapeutic medication monitoring at six months looking at levels in blood samples.

According to the American Heart Association, heart failure is a serious, long-term condition. It's more likely to happen as you age, but anyone can get it. Heart failure cases have been rising in the U.S. due in part to the aging population. About 6.7 million adults in the U.S. are living with heart failure-and expected to increase to more than 8 million by 2030. Heart failure with reduced ejection fraction (HFrEF) means the individual's ejection fraction is equal to or less than 40%, indicating percentage of blood that leaves the left ventricle with each heartbeat. Left ventricular ejection fraction (LVEF) is a metric typically used in heart failure assessments, as it defines the percentage of blood pumped from the left ventricle of the heart to the other organs in the body.

Co-authors, disclosures and funding sources are listed in the manuscript.

Statements and conclusions of studies that are presented at the American Heart Association's scientific meetings are solely those of the study authors and do not necessarily reflect the Association's policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. Abstracts presented at the Association's scientific meetings are not peer-reviewed, rather, they are curated by independent review panels and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting. The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal.

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Additional Resources:

• Multimedia is available on the right column of the release link
• View the abstract in the American Heart Association Scientific Sessions 2025 Online Program Planner
• American Heart Association health information: Managing Heart Failure Symptoms
• American Heart Association guideline: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure
• American Heart Association patient initiative: New initiative launched to improve care for people with certain types of heart failure | American Heart Association
• American Heart Association news release: Spironolactone, a blood pressure medication, may help reduce risk of new heart failure | American Heart Association (Nov. 2024)
• About Scientific Sessions 2025
• For more news at the American Heart Association's Scientific Sessions 2025, follow us on X @HeartNews,#AHA25

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