Polypill Strategy Improves Cardiac Function in HFrEF Trial

A once-daily polypill strategy improved cardiac function compared with enhanced usual care in adults with heart failure with reduced ejection fraction (HFrEF), according to results from the POLY-HF randomized trial published in Nature Medicine.

The open-label trial evaluated whether a polypill containing multiple components of guideline-directed medical therapy (GDMT) could improve left ventricular ejection fraction (LVEF) and related outcomes. The investigators noted that although GDMT reduces morbidity and mortality in HFrEF, real-world use remains low.

The trial enrolled 212 adults with heart failure and LVEF of 40% or lower at 2 centers serving a predominantly underserved population. Participants were randomly assigned to receive a once-daily polypill containing metoprolol succinate, spironolactone 12.5mg, and empagliflozin 10mg, or rapid uptitration of individual GDMT medications, described as enhanced usual care. Participants also continued treatment with a renin-angiotensin system inhibitor or sacubitril/valsartan as a separate pill.

At 6 months, follow-up cardiac magnetic resonance imaging data were available for 187 participants included in the modified intention-to-treat analysis. The polypill group had greater improvement in LVEF compared with enhanced usual care, with a between-group difference of 3.3 percentage points (95% CI, 0.2–6.4; P=.039). The polypill strategy was also associated with a lower rate of heart failure hospitalization or emergency department visits (adjusted rate ratio, 0.40; 95% CI, 0.18–0.88; P=.024).

Medication adherence, assessed through blood concentrations of metoprolol and spironolactone, was higher in the polypill group than in the enhanced usual care group (79% vs 54%; P=.001). The authors reported that the polypill was well tolerated and associated with fewer adverse events than enhanced usual care.

Sources: Pandey A, Keshvani N, Rizvi SK, et al. Polypill for heart failure with reduced ejection fraction: the POLY-HF randomized trial. Nat Med. Published online July 2, 2026. doi:10.1038/s41591-026-04504-5