Rationale, Design, and Baseline Characteristics of the Polypill for Heart Failure With Reduced Ejection Fraction...

Despite the efficacy of guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF), real-world utilization remains suboptimal. Polypill strategies have been trialed for the prevention of atherosclerotic conditions but not in HF.

The Polypill for Heart Failure (POLY-HF) trial was a 2-center, open-label randomized clinical trial conducted within a safety-net health care system and at a university hospital in Dallas, Texas (NCT04633005). Eligible participants were adults with HFrEF (left ventricular ejection fraction [LVEF] ≤40%) not receiving target dose GDMT. Participants were randomized 1:1 to once-daily overencapsulated polypill with multiple dose formulations (metoprolol succinate 25/50/100/150 mg, spironolactone 12.5 mg, empagliflozin 10 mg) vs enhanced usual care with individual GDMTs coordinated with outpatient cardiology/primary care. The primary endpoint was LVEF at 6 months adjusted for baseline, assessed by cardiac magnetic resonance imaging, and the secondary endpoints included a hierarchical composite win-ratio-based endpoint and changes in quality of life, adherence assessed by therapeutic drug monitoring, and N-terminal pro-brain natriuretic peptide (NT-proBNP).

The study enrolled 212 participants (108 polypill, 104 usual care). The median age of the study population was 54 years, with 54% of participants of self-reported Black race and 33% of self-reported Hispanic ethnicity. Participants had a high burden of socioeconomic vulnerability, with 68% uninsured or relying on county indigent health programs, along with frequent food insecurity and housing instability. Baseline clinical characteristics included a median screening LVEF of 25% by echocardiography, a median NT-proBNP of 958 pg/mL, and 85% experiencing recent HF hospitalization. Forty-eight percent of participants received quadruple GDMT prescriptions at baseline, and 73% reported moderate-to-low medication adherence at baseline on a standardized assessment.

POLY-HF enrolled a diverse population with low socioeconomic status and suboptimal medication adherence. This trial will provide the first randomized evidence of polypill effectiveness on biologic and clinical outcomes in HFrEF among underrepresented populations.