Heart failure polypill boosts adherence and cardiac function

Clinical takeaway: For patients with HFrEF who struggle with pill burden or incomplete guideline-directed medical therapy, consolidating a beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor into one daily capsule—while continuing a renin–angiotensin system inhibitor separately—may improve adherence and treatment optimization. Larger, longer-term trials are needed before routine adoption.

Simplifying guideline-directed therapy may help more patients with HFrEF receive and sustain all four recommended medication classes, potentially narrowing a major implementation gap.

In the open-label POLY-HF trial, investigators randomized 212 adults with symptomatic heart failure and an ejection fraction of 40% or less to a once-daily polypill strategy or rapid optimization of separately prescribed medications. Participants had a median age of 54 years; 54% were Black, 33% were Hispanic, and 68% were uninsured or covered through county indigent programs.

At 6 months, cardiac MRI showed an average ejection fraction of 40.4% with the polypill versus 37.1% with enhanced usual care—a 3.3-percentage-point advantage. Heart failure hospitalizations or emergency visits occurred at rates of 37.0 versus 85.8 events per 100 person-years, representing a 60% reduction with the polypill. All-cause hospitalization rates were 53% lower.

Blood testing detected all assessed medications in 79% of polypill recipients, compared with 54% of controls. By month 6, 97% versus 78% were receiving all four recommended drug classes, while 71% versus 42% reached the trial’s threshold for optimal-dose therapy. Quality-of-life scores improved by an additional 8.5 points with the polypill.

Serious adverse events were less frequent with the polypill, although dizziness and genitourinary infections occurred more often. Kidney function and potassium levels were similar between groups.

“POLY-HF shows that simplifying how these drugs are delivered can close that gap,” senior author Thomas J. Wang, MD, said.

Source: Pandey A, et al. (2026 July 2) Nat Med. Polypill for heart failure with reduced ejection fraction: the POLY-HF randomized trial