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Semaglutide in Patients With the Obesity HFpEF Phenotype
Quick Takes
- This prespecified analysis of patients randomized in the STEP-HFpEF trial reports that semaglutide consistently improved HF-related symptoms and physical limitations across the range of LVEF, including in participants with LVEF ≥60%.
- Overall, these data support the potential use of semaglutide in patients with the obesity phenotype of HFpEF regardless of EF.
- Given some limitations of the current analysis, additional prospective and adequately powered studies are indicated to assess the benefit of semaglutide in patients with obesity phenotype of HFpEF with and without type 2 diabetes.
Study Questions:
What are the effects of semaglutide across the baseline left ventricular ejection fraction (LVEF) strata in patients with the obesity phenotype of heart failure with preserved ejection fraction (HFpEF)?
Methods:
The investigators assessed the effects of semaglutide across the baseline LVEF strata in patients with the obesity phenotype of HFpEF in the STEP-HFpEF (Semaglutide Treatment Effect in People With Obesity and HFpEF) trial. STEP-HFpEF randomized 529 patients (263 semaglutide; 266 placebo). For this prespecified analysis, patients were categorized into three groups based on LVEF: 45-49% (n = 85), 50-59% (n = 215), and ≥60% (n = 229). The primary aim of the study was to investigate the effects of semaglutide 2.4 mg once weekly on symptoms, physical limitations, and body weight compared with placebo. Subgroup analyses within the LVEF subgroups for continuous endpoints were then performed using ANCOVA (analysis of covariance) models with 1,000 multiple imputations, adjusted for the baseline values for the relevant continuous outcome variable and body mass index group (the stratification factor).
Results:
At 52 weeks, semaglutide improved the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) (estimated treatment difference [95% confidence interval]: EF 45-49%: 5.0 [-2.7, 12.8], EF 50-59%: 9.8 [5.0, 14.6], and EF ≥60%: 7.4 points [2.8, 12.0]; p for interaction = 0.56) and body weight (EF 45-49%: -7.6 [-10.7, -4.4], EF 50- 59%: -10.6 [-12.6, -8.6], and EF ≥60%: -11.9% [-13.8, -9.9]; p for 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 difference (p for interaction = 0.19), hierarchal composite endpoint (p for interaction = 0.43), and C-reactive protein (p for interaction = 0.26); or exploratory endpoint of N-terminal pro–B-type natriuretic peptide (p for interaction = 0.96). Semaglutide was well-tolerated across LVEF categories.
Conclusions:
The authors report that 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.
Perspective:
This prespecified analysis of the 529 patients randomized in the STEP-HFpEF trial reports that semaglutide consistently improved HF-related symptoms and physical limitations, as well as exercise function, and reduced body weight and inflammation across the range of LVEF, including in participants with LVEF ≥60%. Overall, these data support the potential use of semaglutide in patients with the obesity phenotype of HFpEF regardless of EF. Given some limitations of the current analysis, additional prospective and adequately powered studies are indicated to assess the benefit of semaglutide in patients with obesity phenotype of HFpEF with and without type 2 diabetes.
Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure
Keywords: Heart Failure, Glucagon-Like Peptide 1, Metabolic Diseases, Obesity, Stroke Volume
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