A Huge Win for Patients With HFpEF and Obesity

Relative to patients with heart failure with preserved ejection fraction (HFpEF), patients with heart failure with reduced ejection fraction (HFrEF) are relatively spoiled. Those with HFrEF have access to 4 classes of life-prolonging medications, many of which have been around since the early 2000s. Patients with HFpEF have only recently had a win, with the identification of SGLT2 inhibitors as important medications to reduce the composite endpoint of mortality or hospitalization for heart failure.

The tide is slowly turning for patients with HFpEF. In a recent edition of this column, we explored some new data suggesting that finerenone might improve outcomes for these patients. Additionally, a recent study showed that semaglutide can improve quality-of-life scores and promote weight loss in patients with obesity and HFpEF.

Talking Point: Tirzapatide Scores a Big Win

In a new trial, 731 patients with HFpEF and obesity were randomly assigned to receive tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks. The 2 primary endpoints were a composite of adjudicated death from cardiovascular causes or a worsening heart-failure event.

Death from cardiovascular causes or a worsening heart-failure event occurred in 36 patients (9.9%) in the tirzepatide group compared with 56 patients (15.3%) in the placebo group (HR, 0.62; 95% CI, 0.41 to 0.95; P = 0.026). Patients randomized to tirzapatide experiences improvements in quality-of-life scores but also a higher rate of adverse gastrointestinal events leading to study drug discontinuation.

Talking Point: An Exciting Step Forward

HFpEF remains an underserved patient population in terms of available life-saving therapies. This new evidence is the first to suggest that the GLP-1 class of medications may mitigate the high residual disease burden for patients with obesity and HFpEF. Larger studies would be helpful in confirming these early findings, as would studies examining the use of these medications in nonobese patients with HFpEF. At the moment, it is not clear how much of the benefit seen in this trial was due to the weight loss that the patients experienced versus other pleotropic benefits that this class might hold.