In adults with HF with preserved ejection fraction and obesity, tirzepatide reduced a composite of CV death or worsening HF at 2 y
A manufacturer trial added to the evidence that incretin-based therapies improve cardiovascular (CV) outcomes in patients with obesity and heart failure (HF) with preserved ejection fraction, regardless of the presence of diabetes, an ACP Journal Club commentary said.
Tirzepatide improved outcomes over placebo in patients with heart failure with preserved ejection fraction (HFpEF), according to a manufacturer-funded study. The international trial, called SUMMIT, included 731 patients with obesity and heart failure with an ejection fraction of at least 50% (48% with type 2 diabetes [T2D]) randomized to tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks. The primary end points were a composite of death from cardiovascular causes or a worsening heart failure event and change from baseline to 52 weeks in quality of life (QoL).
The study was published by the New England Journal of Medicine on Nov. 16, 2024. The following commentary by Leslie A. Ynalvez, MD, and Anita Deswal, MD, MPH, was published in the ACP Journal Club section of Annals of Internal Medicine on April 1.
Obesity plays a key role in the incidence and morbidity of HFpEF through several postulated mechanisms, including inflammation, paracardiac adiposity, cardiac lipotoxicity, insulin resistance, microvascular dysfunction, and cardiac remodeling, along with shared comorbid conditions. Tirzepatide, an agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptors, is approved in the USA for weight loss in persons with obesity or with overweight and a weight-related comorbidity, and for glycemic control in T2D.
Two recent trials in the STEP-HFpEF program of 1,145 patients with obesity and HFpEF, with and without T2D, found that semaglutide reduced weight (−8.4%) and improved QoL at 1 year vs. placebo; walk distance increased and inflammation (C-reactive protein [CRP]) and natriuretic peptide levels were reduced. Although HF hospitalization or urgent HF visits were lower with semaglutide, the overall number of events was modest.
The 2-year SUMMIT trial enrolled 731 patients with obesity and HFpEF, with nearly half having an HF-related hospitalization or urgent care visit in the previous year. Weight loss was greater with tirzepatide than with placebo, and there was a definitive reduction in the primary outcome of CV death or worsening HF, driven by a reduction in worsening HF events. Again, CRP, QoL, and function improved with tirzepatide. Taken together, these trial results suggest that incretin-based therapies are effective for weight loss, HF outcomes, and health status in patients with obesity-associated HFpEF, regardless of the presence of T2D. Maintenance of weight loss requires continued use of these drugs, and gastrointestinal side effects are still a challenge. At present, no data support a benefit on HF outcomes in patients with HF with reduced EF or HFpEF without obesity.