Effects of semaglutide in obesity‐related heart failure with preserved ejection fraction across the age spectrum: Findings from the STEP ‐ HFpEF programme

Abstract Background The prevalence of heart failure with preserved ejection fraction (HFpEF) increases with age, and older adults with HFpEF have worse physical function, quality of life, and clinical outcomes. Semaglutide demonstrated efficacy in the treatment of obesity‐related HFpEF in the STEP‐HFpEF trials. Some have speculated that older patients may have less to gain from incretin therapies (and perhaps more to lose) than younger patients. Aims In this pre‐specified pooled subanalysis of the STEP‐HFpEF trials, we evaluated the efficacy of semaglutide across the age spectrum. Methods The STEP‐HFpEF and STEP‐HFpEF DM trials enrolled participants with obesity‐related HFpEF and randomized them to semaglutide 2.4 mg once weekly ( n = 573) or placebo ( n = 572) for 52 weeks. Dual primary outcomes (change in Kansas City Cardiomyopathy Questionnaire clinical summary score [KCCQ‐CSS] and change in body weight) and secondary outcome measures (6‐minute walk distance [6MWD], C‐reactive protein, hierarchical composite endpoint containing all‐cause death, heart failure events, changes in KCCQ‐CSS and 6MWD) were compared across specific age groups; <55 years, 55–64 years, 65–74 years and ≥75 years. Results Among 1145 randomized participants, 8.8% ( N = 101) were <55, 23.3% ( N = 267) were aged between 55–64, 42.4% ( N = 485) were between 65–74, and 25.5% ( N = 292) were 75 years or over. The efficacy of semaglutide on the dual primary endpoints was consistent across the age spectrum, KCCQ‐CSS ( p ‐interaction = 0.80), and body weight ( p ‐interaction = 0.41). Similar benefits were observed for the key secondary endpoints, with no treatment effect heterogeneity across age groups. Moreover, the safety of semaglutide was consistent across age groups. Conclusion In patients with HFpEF enrolled across the STEP‐HFpEF and STEP‐HFpEF DM trials, treatment with semaglutide improved disease‐specific symptoms, physical function and reduced body weight across the age spectrum. The safety profile of semaglutide was consistent in older and younger patients.