Abstract Body (Do not enter title and authors here): Background: Heart failure with reduced ejection fraction (HFrEF) disproportionately affects patients of minoritized racial/ethnic groups with adverse social determinants of health (SDOH). Despite efficacy of HFrEF guideline-directed medical therapy (GDMT), real-world utilization remains suboptimal in underserved communities. Polypill strategies have been trialed for prevention of atherosclerotic conditions but not in HFrEF.
Hypothesis: We hypothesized that an HFrEF polypill containing metoprolol succinate, spironolactone, and empagliflozin would improve left ventricular ejection fraction (LVEF) compared with usual care in patients.
Methods: POLY-HF is a two-center, open-label RCT conducted primarily within a safety-net healthcare system in Dallas, TX (NCT04633005). Eligible participants were adults with HFrEF (LVEF≤40%) not receiving target dose GDMT. Participants were randomized 1:1 to once-daily over-encapsulated polypill with multiple dose formulations (metoprolol succinate 25/50/100/150 mg, spironolactone 12.5 mg, empagliflozin 10 mg) with separate renin-angiotensin system inhibitor vs usual care with individual GDMTs coordinated with outpatient cardiology/primary care. The primary endpoint is change in cardiac MRI-based LVEF from baseline to six months. Key secondary endpoints include changes in NT-proBNP, quality of life, and clinical outcomes.
Results/Data: Enrollment of 212 participants (108 polypill, 104 usual care) has completed. The population was young (median 54 years) and diverse, with 54% Black race, 33% Hispanic ethnicity, and 20% Spanish-speaking (Table). Participants reported high burden of adverse SDOH, with 68% uninsured or relying on county indigent health programs, 43% experiencing food insecurity, and 32% reporting housing instability. Clinical characteristics included median baseline LVEF of 26% by cardiac MRI, median NT-proBNP of 958 pg/mL, a high comorbidity burden, and 85% experiencing recent HF hospitalization. Despite 48% receiving quadruple GDMT prescriptions at baseline, 73% demonstrated moderate-to-low medication adherence on standardized assessment.
Conclusions: POLY-HF enrolled a diverse population with high burden of adverse SDOH and poor medication adherence. Database lock is anticipated in October 2025, and complete results will be presented at the meeting. This trial will provide the first randomized evidence for polypill effectiveness on biologic and clinical outcomes in HFrEF among underrepresented populations.