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Cohosts Stephen Greene, MD, and Muthiah Vaduganathan, MD, sat down with Ambarish Pandey, MD, to discuss the revolutionary POLY-HF trial and how polypills can fit into heart failure treatment.
Welcome back to Don't Miss a Beat!
In this episode of Don’t Miss a Beat, cohosts Steven Green, MD, and Muthu Vaduganathan, MD, MPH, sit down with Ambarish Pandey, MD, from UT Southwestern, to discuss the landmark POLY-HF trial, presented at the 2025 American Heart Association Scientific Sessions in New Orleans. The discussion centers on the novel concept of a “polypill” approach for patients with heart failure with reduced ejection fraction (HFrEF), aiming to simplify guideline-directed medical therapy (GDMT) and improve adherence while maintaining safety and efficacy.
00:00:00 Introduction
00:00:45 Polypills in cardiovascular medicine
00:02:32 Structuring the POLY-HF trial
00:05:00 Mechanics of POLY-HF
00:07:43 The patient population in POLY-HF
00:09:47 Dosing other medications in POLY-HF
00:11:54 Results of POLY-HF
00:14:57 Reaching endpoints in POLY-HF
00:18:52 Safety in POLY-HF
00:22:09 Upcoming studies
00:23:54 Outro
Pandey outlines how the POLY-HF trial was designed to test whether a single encapsulated pill combining three GDMT classes - metoprolol succinate, spironolactone, and empagliflozin - could enhance treatment adherence and cardiac function compared to enhanced usual care. Conducted at UT Southwestern and Parkland Hospital, the study enrolled 212 patients with HFrEF (EF <40%), a population notably enriched with individuals from socioeconomically disadvantaged backgrounds, over half of whom self-identified as Black and nearly one-third as Hispanic. Participants were randomized to receive either the polypill or enhanced usual care, with structured follow-up at one, three, and six months, and primary evaluation by cardiac MRI at six months.
Results demonstrated significant benefits with the polypill strategy. Patients in the polypill arm experienced a 3.4% greater improvement in left ventricular ejection fraction compared with those in usual care, along with a 50% reduction in recurrent heart failure hospitalizations or emergency visits. The quality of life, as measured by patient-reported outcomes, improved by nearly nine points compared to usual care. Most notably, therapeutic drug monitoring revealed a 50% higher adherence rate to prescribed therapies in the polypill group, confirming the intervention’s mechanistic rationale. Rates of optimal-dose quadruple GDMT use also exceeded 90% in the polypill group compared with approximately 70% in usual care.
Safety outcomes were reassuring, with no excess in hyperkalemia, renal dysfunction, or treatment discontinuation observed. Mild hypotension and dizziness were the only slightly increased adverse events. Pandey emphasized that this study, one of the first randomized controlled trials of a polypill in heart failure, demonstrates that multi-drug initiation can be both feasible and safe, even in high-risk, underserved populations.
The episode concludes with reflections on how POLY-HF complements prior rapid-sequencing trials such as STRONG-HF and may reshape real-world practice by simplifying GDMT delivery. Pandey notes that a larger multicenter outcomes trial is already underway to confirm these findings and advance the potential for polypill-based therapy to transform heart failure management.
Relevant disclosures for Vaduganathan include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others. Relevant disclosures for Greene include Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others. Relevant disclosures for Pandey include Lilly USA, Cytokinetics, Roche Diagnostics, Merck, Bayer, Novo Nordisk, and others.
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