Dr. Ambreen Mohamed and Dr. C. Michael Gibson Discuss: POLY-HF — A Polypill Strategy for Heart Failure with Reduced Ejection Fraction

In this episode of SnackableHealth™, Dr. C. Michael Gibson talks with Dr. Ambreen Mohamed about the POLY-HF trial, a NIH-funded, randomized, controlled study testing whether consolidating key heart failure therapies into a single capsule could improve adherence, uptake, and outcomes for patients with heart failure with reduced ejection fraction (HFrEF).

The rationale is simple yet powerful: patients with HFrEF often face pill fatigue and therapeutic inertia, juggling multiple medications that each require titration and monitoring. Despite robust evidence supporting the “four pillars” of care — beta-blockers, MRAs, SGLT2 inhibitors, and ARNI/ACEi — real-world adherence remains suboptimal. The POLY-HF trial sought to test whether a “one-capsule strategy” could overcome these barriers.

A total of 212 patients were enrolled and randomized to receive either standard up-titration care or a once-daily encapsulation-based polypill containing metoprolol succinate (25–150 mg), spironolactone (12.5 mg), and empagliflozin (10 mg). ACEi/ARNI therapy remained external to ensure once-daily dosing feasibility. Unlike traditional fixed-dose combinations, this capsule approach simply co-encapsulated approved agents — removing much of the regulatory complexity and allowing in-pharmacy compounding.

After 6 months, results were compelling:

• Left ventricular ejection fraction (LVEF) improved by an additional 3.6 percentage points versus enhanced usual care, measured by cardiac MRI.
• Quality-of-life scores improved by ~9 points, reflecting better daily functioning and symptom control.
• Heart-failure hospitalizations and emergency visits were reduced by 60% in the polypill arm.
• Adherence, verified by serum drug-level testing (HPLC assays for metoprolol and spironolactone), was 4-fold higher in the polypill group.

Beyond numbers, the study revealed an operational victory: >90% of patients in the polypill arm achieved all four GDMT pillars at any dose — compared with ~70% under enhanced usual care. This suggests that simplification, not just education, drives implementation.

Dr. Gibson praised the trial as a “real-world innovation that adds life to years and years to life.” Dr. Mohamed emphasized that the approach could democratize access by leveraging local pharmacy encapsulation rather than relying solely on industry manufacturing. For systems overwhelmed by polypharmacy, POLY-HF reframes adherence as an engineering challenge — solvable through simplicity.