Wegovy improves exercise function in obesity-related HF with concomitant weight loss
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Key takeaways:
- Wegovy improved exercise function among patients with obesity-related heart failure with preserved ejection fraction.
- The greatest improvements were observed in those with the most weight lost at 52 weeks.
Semaglutide 2.4 mg was linked to early, sustained improvement in exercise function among patients with obesity-related HF and improved most among those with the largest proportionate weight loss, a speaker reported.
The results of a secondary analysis of the pooled STEP-HFpEF and STEP-HFpEF DM trials were presented at a virtual late-breaking clinical research session of the Heart Failure Society of America Annual Scientific Meeting. The in-person meeting was canceled due to Hurricane Helene.
“We know that heart failure with preserved ejection fraction now represents the majority of heart failure cases in the community, and among those with heart failure with preserved ejection fraction, the majority are also living with overweight or obesity,” Mikhail Kosiborod, MD, FACC, FAHA, cardiologist at Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri-Kansas City School of Medicine, said during a presentation. “Previous studies have demonstrated that among patients with obesity-related HFpEF, those patients experience worse burden of symptoms, physical limitations and a greater degree of exercise impairment.
“The objective of this prespecified secondary analysis of the pooled STEP-HFpEF and STEP-HFpEF diabetes trials comprising the STEP-HFpEF program, was to evaluate the efficacy of once-weekly semaglutide 2.4 mg on 6-minute walking distance ... And also evaluate the change in 6-minute walking distance according to magnitude of weight loss,” he said.
The STEP-HFpEF and STEP-HFpEF DM trials included 1,145 adult patients with HFpEF and BMI of 30 kg/m2 or more; those in STEP-HFpEF did not have diabetes and those in STEP-HFpEF DM did. Participants were randomly assigned to once-weekly semaglutide 2.4 mg (Wegovy, Novo Nordisk) or placebo. The dual primary endpoints were change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score and body weight from baseline to 52 weeks.
As Healio previously reported, semaglutide 2.4 mg was associated with significant improvement of HF symptoms and physical function compared with placebo.
For the present subanalysis, Kosiborod and colleagues evaluated the efficacy of semaglutide 2.4 mg on 20- and 52-week change in 6-minute walk distance across subgroups and based on weight loss as well as impact of baseline walk distance on the primary and key secondary endpoints.
Participants were grouped into one of three tertiles of increasing 6-minute walk distance at baseline.
Overall, participants in the lowest tertile of 6-minute walk distance at baseline were more often older with higher waist circumference, BMI, C-reactive protein and N-terminal pro-B-type natriuretic peptide. These patients also had higher NYHA class and lower KCCQ scores. Left ventricular ejection fraction was not significantly different between tertiles of baseline walk distance.
Early improvement in 6-minute walk distance was observed among participants assigned to semaglutide 2.4 mg compared with placebo at 20 weeks (estimated treatment difference, 14.6 m; 95% CI, 8.6-20.7) and were sustained out to 52 weeks (estimated treatment difference, 17.1 m; 95% CI, 9.2-25; P for both < .0001), Kosiborod said during the presentation. Improvement in walk distance was consistent across all patient subgroups.
Kosiborod and colleagues noted that the estimated mean difference in 6-minute walk distance increased further among patients’ with a proportionately larger decreases in body weight from baseline to week 52:
- less than 5% decrease (0.1 m; 95% CI, 5.1 to 5.3);
- 5% to 10% decrease (17.1 m; 95% CI, 9.9-24.30;
- 10% to 15% decrease (22.2 m; 95% CI, 14-30.50;
- 15% to 20% decrease (24.3 m; 95% CI, 13.6-35); and
- 20% or more decrease (34.7 m; 95% CI, 23-46.5)
Moreover, the benefits of semaglutide 2.4 mg on key secondary endpoints such as a hierarchical composite endpoint and C-reactive protein ratio were also consistent across all tertiles of baseline 6-minute walk distance, with fewer serious and cardiac adverse events.
“In patients with obesity-related HFpEF, baseline impairment in exercise function was associated with greater inflammation, congestion and adiposity. Semaglutide improved 6-minute walking distance as early as 20 weeks, preceding maximal weight loss, with a sustained effect at 52 weeks that was consistent across a variety of demographic and clinical subgroups, with no evidence of heterogeneity,” Kosiborod said during the presentation. “Greater magnitude of weight loss was associated with larger improvements in 6-minute walking distance, regardless of treatment assignment. Semaglutide-mediated improvements in HF-related symptoms, physical limitations and exercise function, as well as reductions in inflammation, congestion and body weight were all consistent regardless of baseline exercise function ... Semaglutide was well tolerated across the spectrum of 6-minute walking distance, with lower rates of serious adverse events and cardiac adverse events compared with placebo.”
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Pandey A, et al. Late breaking clinical research session I. Presented at: The Heart Failure Society of America Annual Scientific Meeting; Sept. 27-30, 2024 (virtual meeting).
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