Semaglutide beneficial for patients with HFpEF and obesity

medwireNews: Results from the STEP-HFpEF trial suggest that patients with heart failure with preserved ejection fraction (HFpEF) and obesity could benefit from treatment with semaglutide 2.4 mg/week. Semaglutide “led to larger reductions in symptoms and physical limitations, greater improvements in exercise function, and greater weight loss than placebo,” write the researchers in a publication accompanying the presentation at the ESC Congress 2023 in Amsterdam, the Netherlands. They add in The New England Journal of Medicine that semaglutide treatment was associated with fewer serious adverse events (AEs) than placebo and comparable rates of serious AE-related discontinuation. The team therefore believes that the glucagon-like peptide (GLP)-1 receptor agonist “may represent a valuable therapeutic approach” in this patient population. In the double-blind study, 529 individuals with a left ventricular ejection fraction of at least 45% and a BMI of at least 30 kg/m2 were randomly assigned to receive subcutaneous semaglutide 2.4 mg or placebo once a week for 52 weeks, with a further 5 weeks of follow-up. The median age of the participants was 69 years and the majority were women (56.1%) and White (95.8%). For the co-primary endpoint of the mean change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at week 52, semaglutide treatment in 263 patients achieved an increase of 16.6 points compared with 8.7 points for 266 patients given placebo, equating to a significant estimated difference of 7.8 points. The other primary endpoint was change in bodyweight and this was significantly greater at week 52 with semaglutide than placebo, with mean percentage reductions of 13.3% and 2.6%, respectively, and an estimated difference of 10.7 percentage points. Semaglutide treatment was also associated with a significant increase in the 6-minute walk distance relative to placebo, at an average of 21.5 m versus 1.2 m (estimated difference of 20.3 m). And the GLP-1 receptor agonist “produced more wins” in an analysis of a hierarchical composite endpoint comprising death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance, report Mikhail Kosiborod (Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, USA) and colleagues. Finally, the mean percentage reduction in C-reactive protein levels at week 52 was significantly greater in the semaglutide than placebo group, at 43.5% and 7.3%, respectively. With respect to the safety profile, serious AEs occurred in 13.3% of semaglutide-treated participants and 26.7% of those given placebo, a significant difference that was driven largely by the lower number of cardiac disorder events in the semaglutide arm (2.7 vs 11.3%). Six patients in each group discontinued treatment due to serious AEs, with a respective 13.3% and 5.3% of participants discontinuing due to any AE. There were seven deaths during the course of the trial, three in the semaglutide group and four in the placebo group, but just one death in the placebo arm was cardiovascular related. The author of a linked editorial says that “[t]he encouraging findings for semaglutide in patients with heart failure with preserved ejection fraction reported here potentially add a much needed extra option for these patients and provide another upstream treatment for patients with signs of this condition plus a high BMI.” Yigal Pinto, from the University of Amsterdam in the Netherlands, continues: “How these findings translate to hard end points remains to be established and will be important in determining the role of GLP-1 agonism as compared with [sodium-glucose cotransporter 2] inhibition in patients with heart failure with preserved ejection fraction.” medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group ESC Congress 2023; Amsterdam, the Netherlands: 25–28 August N Engl J Med 2023; doi:10.1056/NEJMoa2306963 N Engl J Med 2023; doi:10.1056/NEJMe2309294

ERS International Congress 2023

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Semaglutide beneficial for patients with HFpEF and obesity

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ERS International Congress 2023

Springer Medicine

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