Semaglutide improves HF symptoms in patients with obesity across range of preserved EF
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Key takeaways:
- Semaglutide improved HF symptoms and exercise capacity vs. placebo in patients with HFpEF and obesity, across the range of LVEF.
- The GLP-1 receptor agonist also reduced inflammatory markers and body weight.
Semaglutide was associated with improved HF symptoms and exercise capacity and reduced body weight and inflammation among patients with obesity across the range of HF with mildly reduced and preserved ejection fraction, a speaker reported.
The results of a secondary analysis of the STEP-HFpEF trial of semaglutide (Wegovy, Novo Nordisk) in patients with obesity and HFpEF were presented at the Heart Failure Society of America Annual Scientific Meeting and simultaneously published in the Journal of the American College of Cardiology.
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“Patients with heart failure have traditionally been divided into heart failure with reduced and preserved ejection fraction and that thought process has evolved over time, and now we classify them into three different categories: reduced, mildly reduced and preserved ejection fraction. Because of this changing definition, the clinical trials in patients with HFpEF have used various definitions for inclusion criteria of ejection fraction greater than 40%, 45% or 50%,” Healio | Cardiology Today Editorial Board Member Javed Butler, MD, MPH, MBA, FACC, FAHA, FESC, president of the Baylor Scott and White Research Institute, senior vice president for Baylor Scott and White Health and distinguished professor of medicine at the University of Mississippi, said during a presentation. “While the SGLT2 inhibitors have shown to be beneficial across the spectrum of ejection fraction, in the secondary analyses of other therapies that we use in heart failure, the benefits were largely seen in patients with mildly reduced ejection fraction. There is a debate [whether] patients with ejection fraction greater than 60% [benefited from] the therapy or not.”
The STEP-HFpEF trial included 529 adults with HFpEF and a BMI of 30 kg/m2 or more and researchers randomly assigned them once-weekly semaglutide 2.4 mg, a GLP-1 receptor agonist or placebo for 52 weeks.
The dual primary endpoints were change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score and change in body weight.
As Healio previously reported, in the main results of STEP-HFpEF, semaglutide was associated with significant improvement in HF-related symptoms and physical limitations and weight loss in adult patients with HFpEF and obesity compared with placebo.
For the present study, Butler and colleagues stratified the study participants by baseline left ventricular ejection fraction and reevaluated the dual primary endpoints of the STEP-HFpEF trial as well as confirmatory secondary endpoints, including change in 6 minute walk distance, a hierarchical composite of time to all-cause death, number of and time to HF hospitalization, difference in change in KCCQ score and change in C-reactive protein.
Overall:
- 85 patients had LVEF of 45% to 49% (mean age, 69 years; 35% women; 99% white);
- 215 had LVEF of 50% to 59% (mean age, 69 years; 55% women; 97% white); and
- 229 had LVEF of 60% or more (mean age, 70 years; 65% women; 93% white).
Patients with LVEF of 50% to 59% were more likely to have a HF hospitalization within 1 year compared with those with higher or lower LVEF (P = .04), and those with LVEF between 45% and 49% were more likely to have CAD (P = .03) than those in the other groups.
Compared with the other groups, patients with LVEF between 45% and 49% were more likely to be prescribed concomitant medications including diuretics (P < .001), mineralocorticoid receptor antagonists (P = .02); ACE inhibitors/angiotensin receptor blockers (P = .02) and angiotensin receptor-neprilysin inhibitors (P = .02).
Butler reported a significant reduction in body weight from baseline to 52 weeks across all LVEF ranges, with an overall average reduction of 10.7 percentage points compared with placebo (P overall < .001; P for interaction between LVEF groups = .08).
In addition, semaglutide was associated with improvement in KCCQ clinical summary score across LVEF groups compared with placebo (estimated treatment differences: 5 points for EF 45% to 49%; 9.8 points for EF 50% to 59%; 7.4 points for EF 60% or more; P for interaction = .56), according to the researchers.
The researchers observed a mean improvement in 6-minute walk distance of 20.3 m compared with placebo (P < .001), which was primarily driven by improvement in the LVEF ranges of 50% to 59% and 60% or more, but the interaction between LVEF groups was not significant (P for interaction = .19).
Analyses of each component of the hierarchical composite resulted in an estimated average win ratio favoring semaglutide over placebo of 1.72 (95% CI, 1.37-2.15; P < .001) for all LVEF ranges (P for interaction = .43).
Moreover, average reductions in CRP (mean treatment ratio, 0.61; 95% CI, 0.51-0.72; P < .001; P for interaction = .26) and N-terminal pro-B-type natriuretic peptide (mean treatment ratio, 0.84; 95% CI, 0.71-0.98; P for interaction = .96) were consistent across all three LVEF subgroups, according to the presentation.
“In patients with heart failure and preserved ejection fraction with obesity, semaglutide 2.4 mg improved symptoms, physical limitation and exercise function and reduced inflammation and body weight to a similar extent across LVEF subgroups,” Butler said during the presentation. “There was no safety concern in any of the LVEF-based subgroups. These data support treatment with semaglutide for improving heart failure-related symptoms, physical limitation, exercise capacity and weight loss in patients with obesity phenotype of HFpEF.”
Reference:
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Butler J, et al. Late breaking clinical trials. Presented at: The Heart Failure Society of America Annual Scientific Meeting; Oct. 6-9, 2023; Cleveland.
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