Stephen J. Greene, MD, FACC, FHFSA

Don't Miss a Beat: POLY-HF & the Potential of Polypills in HF, With Ambarish Pandey, MD

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.

00:00:45 Polypills in cardiovascular medicine

00:07:43 The patient population in POLY-HF

00:09:47 Dosing other medications in POLY-HF

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.

Pandey A, Keshvani N, Rizvi S, et al. A Polypill Strategy for Heart Failure with Reduced Ejection Fraction: The POLY-HF Trial. Presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10, 2025.

Mebazaa A, Davison B, Chioncel O, et al. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial. Lancet. 2022;400(10367):1938-1952. 

Podcasts

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.

Navigating Access Barriers and Treatment Gaps in HFpEF Care

Access to care remains a major determinant of heart failure with preserved ejection fraction (HFpEF) outcomes. Panelists noted that disparities in insurance coverage, drug costs, and specialist availability limit the adoption of newer therapies such as finerenone.

They discussed how expanding formulary access, streamlining prior authorization processes, and improving clinician education can help close these gaps. Collaborative models between cardiology, primary care, and pharmacy teams were highlighted as effective tools for improving access.

Ultimately, addressing systemic barriers is essential for translating clinical advances into real-world benefit. The panel agreed that equity in care delivery must remain a central goal as HFpEF management continues to evolve.

Videos

The discussion concludes with strategies to overcome access barriers and ensure equitable implementation of novel HFpEF therapies.

Challenges With Combining Nonsteroidal MRAs and Treatment Adherence in HFpEF

Panelists discussed that although nonsteroidal mineralocorticoid receptor antagonists such as finerenone offer clear clinical advantages, treatment adherence remains a critical barrier to success. Complex regimens, frequent laboratory monitoring, and adverse effect concerns often hinder consistent use.

They emphasized simplifying care through patient education, digital reminders, and coordinated follow-up. Addressing cost and access issues is equally important to ensuring long-term persistence with therapy.

Panelists concluded that optimizing adherence requires aligning clinical simplicity with patient empowerment. When patients understand their treatment rationale and receive ongoing support, therapy success rates improve significantly.

Panelists address adherence challenges and the need for careful coordination when integrating nonsteroidal MRAs into multifaceted treatment plans.

Strategies for Prevention of HFpEF

Panelists highlighted prevention as the most powerful but underutilized strategy in heart failure with preserved ejection fraction (HFpEF) care. Because the condition often develops from metabolic and hypertensive pathways, early lifestyle modification can delay or prevent disease onset.

They discussed how weight management, exercise, and strict blood pressure control significantly lower HFpEF risk. Early use of cardioprotective agents such as sodium-glucose transporter 2 inhibitors in high-risk populations may also offer preventive benefits.

Panelists concluded that prevention requires both system-level and patient-level commitment. Integrating cardiovascular risk screening into routine care and emphasizing patient education could reduce the growing burden of HFpEF worldwide.

Experts highlight preventive approaches, including risk factor control and early therapeutic intervention, to mitigate HFpEF development.

Stephen J. Greene, MD, FACC, FHFSA

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