Semaglutide Effects According to Ejection Fraction in Heart Failure with Preserved Ejection Fraction and Obesity

Many therapies for heart failure (HF) have shown differential impact across the spectrum of left ventricular ejection fraction (LVEF). In this prespecified analysis, we assessed the effects of semaglutide across the baseline LVEF strata in patients with the obesity phenotype of HF with preserved EF (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 pre-specified analysis, patients were categorized into 3 groups based on LVEF: 45-49% (n=85), 50-59% (n=215) and ≥60% (n=229). At 52 weeks, semaglutide improved the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) (estimated treatment difference [95%CI]: 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 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 interaction =0.08), to a similar extent across LVEF categories. Likewise, LVEF did not influence the benefit of semaglutide on confirmatory secondary endpoints: 6MWD (P interaction= 0.19), hierarchal composite endpoint (P interaction= 0.43), and CRP (P interaction= 0.26); or exploratory endpoint of NT-proBNP (P interaction= 0.96). Semaglutide was well-tolerated across LVEF categories. 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.