Wegovy shows benefit even in patients with high frailty, obesity-related heart failure
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Key takeaways:
- Wegovy improved body weight, exercise capacity and symptoms vs. placebo across the frailty spectrum in patients with obesity-related HFpEF.
- The effects were strongest among participants who were most frail.
Treatment of obesity-related HF with preserved ejection fraction with semaglutide 2.4 mg improved body weight, physical function and HF symptoms regardless of the extent of patient frailty, a speaker reported.
In addition, the benefits of semaglutide 2.4 mg (Wegovy, Novo Nordisk) were strongest in those with the highest levels of frailty, according to data 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.
“Frailty, a syndrome characterized by reduced physiologic reserve and impaired homeostatic tolerance to stressors, is common among patients with HFpEF, with shared pathophysiologic mechanisms, and is associated with poor functional and clinical outcomes,” Ambarish Pandey, MD, associate professor of internal medicine at UT Southwestern Medical Center, said during a presentation. “Whether the safety and efficacy of semaglutide in patients with obesity-related HFpEF vary by frailty status, and the effect of semaglutide on frailty itself over time are unknown.”
The STEP-HFpEF and STEP-HFpEF DM trials included 1,145 adult patients with HFpEF and BMI of 30 kg/m2 or more with and without diabetes. Participants were randomly assigned once-weekly semaglutide 2.4 mg 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 for patients with obesity-related HFpEF, with and without diabetes, was associated with significant improvement of HF symptoms and physical function compared with placebo.
For this STEP-HFpEF subanalysis, Pandey and colleagues evaluated the effects of once-weekly semaglutide 2.4 mg by patient frailty status and its impact on frailty burden during follow-up.
A frailty index was derived using patient medical history, vitals, laboratory data and quality of life questionnaires to stratify patients into one of three groups: nonfrail (n = 110), more frail (n = 343) and most frail (n = 692).
Common characteristics among the participants who were most frail at baseline included female sex, older age, higher BMI, higher burden of HF symptom, lower KCCQ score and impaired exercise capacity.
The researchers reported that benefits of semaglutide 2.4 mg on body weight (P for interaction = .385) and 6-minute walk distance (P for interaction = .141) were consistent across all three frailty groups; however, individuals in the most frail group reported significantly greater improvement in KCCQ clinical summary score at 52 weeks for semaglutide compared with placebo (adjusted mean difference, 11) compared with those designated as more frail (adjusted mean difference, 3.7) and nonfrail (adjusted mean difference, 1.5; P for interaction < .001).
Similar to change in body weight, the 52-week improvements with semaglutide compared with placebo in C-reactive protein (P for interaction = .832) and N-terminal pro-B-type natriuretic peptide (P for interaction = .47) were also comparable across frailty groups, Pandey said during the presentation.
Moreover, frailty improved in more than half of participants assigned to semaglutide 2.4 mg to the extent they were considered nonfrail at 52 weeks, compared with one-third of participants assigned to placebo. Frailty class improvement was more likely to occur with semaglutide compared with placebo (P for interaction < .0001), Pandey said.
“Across increasing frailty strata, semaglutide resulted in a similar reduction in body weight compared with placebo but greater improvements in HF-related symptoms, physical limitations and the hierarchical composite endpoints, particularly with the strongest effect noted among those with the highest frailty burden,” Pandey said during the presentation. “Semaglutide significantly reduced the frailty burden over time in this high-risk patient population, and resulted in fewer serious adverse events than placebo across the frailty strata. These findings support the use of semaglutide as an effective and well-tolerated therapy in the high-risk population of frail patients with obesity-related HFpEF.”
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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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