New Drug Classes Finally Show Promise for Heart Failure With Preserved Ejection Fraction | Research

The takeaway

SGLT2 inhibitors, non-steroidal MRAs, and GLP-1 receptor agonists represent the first effective therapies for HFpEF, a condition that historically lacked disease-modifying treatments.

<25%
of HFpEF patients survive beyond 5 years, but new drug classes now offer hope

What the researchers found

SGLT2 inhibitors, non-steroidal MRAs, and GLP-1 receptor agonists have demonstrated benefits in landmark HFpEF trials, establishing the first effective treatment paradigm for this condition.

Why it matters

HFpEF has been called cardiology's "biggest unmet need" for decades; these new drug classes finally offer patients disease-modifying treatment options.

The numbers in context

~8 million HF patients in US; ~50% have HFpEF; <25% survive beyond 5 years; reviews STEP-HFpEF, SUMMIT, and other landmark trials.

How the study worked

Review of landmark clinical trials and emerging evidence for novel therapeutic classes in HFpEF.

Who was studied

Patients with heart failure with preserved ejection fraction

What this study cannot tell us

Review article; individual trial populations and inclusion criteria differ; long-term outcomes and optimal combination strategies still being studied.

How to read the evidence

Review based on multiple landmark randomized controlled trials providing high-quality evidence for each therapeutic class.

When this study was published

Published in 2025, summarizing the transformative clinical trial results from the past 5 years.

The bigger picture

The convergence of diabetes, obesity, and heart failure treatments reflects a paradigm shift toward recognizing these conditions as interconnected metabolic-cardiovascular diseases requiring integrated therapy.

Questions still open

What is the optimal combination and sequencing of SGLT2i, Ns-MRAs, and GLP-1 RAs in HFpEF?
Do these therapies benefit all HFpEF phenotypes equally, or mainly obesity-related HFpEF?

Common questions

What is HFpEF and why is it so dangerous?

Heart failure with preserved ejection fraction (HFpEF) means the heart pumps normally but stiffens and cannot fill properly. It affects about half of all heart failure patients and had no effective treatments until recently — with fewer than 25% surviving past 5 years.

How do GLP-1 drugs help heart failure?

GLP-1 receptor agonists appear particularly beneficial for obesity-related HFpEF, reducing body weight, inflammation, and metabolic dysfunction while providing direct cardiovascular benefits. They represent one of three new drug classes transforming HFpEF care.

Read the original research

Heart failure with preserved ejection fraction therapeutics: in search of the pillars.

Heart failure reviews, 30(5), 1005-1014

View on PubMed ↗Publisher’s paper ↗

Citation

Rafei, Abdelghani El; Harrington, Josephine A; Tavares, Caio A M; Guimarães, Patrícia O; Ambrosy, Andrew P; Bonaca, Marc P; Sauer, Andrew J; Vardeny, Orly; Canonico, Mario Enrico. (2025). Heart failure with preserved ejection fraction therapeutics: in search of the pillars.. Heart failure reviews, 30(5), 1005-1014. https://doi.org/10.1007/s10741-025-10524-z