Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction
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Published on: March 29, 2024
Javed Butler1, Steen Z Abildstrøm2, Barry A Borlaug3
1Baylor Scott and White Research Institute, Dallas, Texas, USA; University of Mississippi, Jackson, Mississippi, USA.
Insights
Semaglutide effectively improved heart failure with preserved ejection fraction (HFpEF) symptoms and physical function in obese patients, regardless of left ventricular ejection fraction (LVEF) levels. The treatment demonstrated consistent benefits across all LVEF categories, supporting its use in this population.
Area of Science:
- Cardiology
- Pharmacology
- Metabolic Diseases
Background:
- Heart failure (HF) therapies often have varied effects based on left ventricular ejection fraction (LVEF).
- Obesity is a significant factor in HF with preserved ejection fraction (HFpEF).
Purpose of the Study:
- To assess the efficacy of semaglutide in HFpEF patients with obesity across different LVEF strata.
- To analyze semaglutide's impact on symptoms, physical limitations, and body weight in HFpEF patients stratified by LVEF.
Main Methods:
- A prespecified analysis of the STEP-HFpEF trial involving 529 patients with HFpEF and obesity.
- Patients were categorized into three LVEF groups: 45%-49%, 50%-59%, and ≥60%.
- Outcomes measured included the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, body weight, 6-minute walk distance, and inflammatory markers.
Main Results:
- Semaglutide significantly improved the primary endpoints (symptoms and body weight) across all LVEF categories.
- Benefits on quality of life, exercise function, and inflammation were consistent regardless of baseline LVEF.
- No significant interaction was observed between LVEF and treatment effect for most secondary endpoints.
Conclusions:
- Semaglutide 2.4 mg is effective in improving symptoms, physical limitations, and exercise function in obese patients with HFpEF.
- The benefits of semaglutide were observed consistently across all LVEF categories, supporting its use irrespective of LVEF.
- Semaglutide was well-tolerated in patients with HFpEF and obesity across the spectrum of LVEF.
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).
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