Semaglutide in patients with obesity and heart failure across mildly reduced or preserved ejection fraction

Abstract: Background
Many therapies for heart failure (HF) have shown differential impact across the spectrum of left ventricular ejection fraction (LVEF).

Objectives
In this prespecified analysis, the authors assessed the effects of semaglutide across the baseline LVEF strata in patients with the obesity phenotype of HF with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF) trial.

Methods
STEP-HFpEF randomized 529 patients (263 semaglutide; 266 placebo). For this prespecified analysis, patients were categorized into 3 groups based on LVEF: 45% to 49% (n = 85), 50% to 59% (n = 215), and ≥60% (n = 229).

Results
At 52 weeks, semaglutide improved the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (estimated treatment difference: EF [ejection fraction] 45%-49%: 5.0 points [95% CI: −2.7 to 12.8 points], EF 50%-59%: 9.8 points [95% CI: 5.0 to 14.6 points], and EF ≥60%: 7.4 points [95% CI: 2.8 to 12.0 points]; P interaction = 0.56) and body weight (EF: 45%-49%: −7.6 [95% CI: −10.7 to −4.4], EF 50%-59%: −10.6 [95% CI: −12.6 to −8.6] and EF ≥60%: −11.9 [95% CI: −13.8 to −9.9]; P interaction = 0.08), to a similar extent across LVEF categories. Likewise, LVEF did not influence the benefit of semaglutide on confirmatory secondary endpoints: 6-minute walk distance (P interaction = 0.19), hierarchal composite endpoint (P interaction = 0.43), and high-sensitivity C-reactive protein (P interaction = 0.26); or exploratory endpoint of N-terminal pro-brain natriuretic peptide (P interaction = 0.96). Semaglutide was well-tolerated across LVEF categories.

Conclusions
In patients with HFpEF and obesity, semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight to a similar extent across LVEF categories. These data support treatment with semaglutide in patients with the obesity phenotype of HFpEF regardless of LVEF. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF]; NCT04788511)

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Journal of the American College of Cardiology. - 82, 22 (2023) , 2087-2096, ISSN: 1558-3597

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2023
• Creator: Butler, Javed ; Abildstrøm, Steen Z. ; Borlaug, Barry A. ; Davies, Melanie ; Kitzman, Dalane W. ; Petrie, Mark C. ; Shah, Sanjiv J. ; Verma, Subodh ; Abhayaratna, Walter P. ; Chopra, Vijay ; Ezekowitz, Justin A. ; Fu, Michael ; Ito, Hiroshi ; Lelonek, Małgorzata ; Núñez, Julio ; Perna, Eduardo ; Schou, Morten ; Senni, Michele ; Meer, Peter J. van der ; von Lewinski, Dirk ; Wolf, Dennis ; Altschul, Rebecca L. ; Rasmussen, Søren ; Kosiborod, Mikhail N.

Further information

• DOI: 10.1016/j.jacc.2023.09.811
• URN: urn:nbn:de:bsz:25-freidok-2415174
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:47 PM CET