Background
Heart failure with preserved ejection fraction has increasing prevalence and is associated with a high symptom burden and functional impairment, especially in people with obesity. No therapies have been approved to address obesity-related heart failure with preserved ejection fraction.
Methods
We randomly assigned 529 patients with heart failure with preserved ejection fraction and a body mass index (weight in kilograms divided by the square of height in meters) of 30 or more to receive semaglutide (2.4 mg) once a week. week or placebo for 52 weeks.
The dual primary endpoints were change from baseline in Kansas City Cardiomyopathies Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations). and change in body weight.
Confirmatory secondary endpoints included change in 6-minute walk distance; a hierarchical composite endpoint that included death, heart failure events, and differences in change in the KCCQ-CSS and 6-minute walk distance; and the change in the level of C-reactive protein (CRP).
Results
The mean change on the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; P<0.001), and the mean percent change in body weight was −13.3% with semaglutide and −2.6% with placebo (estimated difference, −10.7 percentage points; 95% CI, −11.9 a −9.4, P < 0.001).
The mean change in 6-minute walk distance was 21.5 m with semaglutide and 1.2 m with placebo (estimated difference, 20.3 m; 95% CI, 8.6 to 32.1; P <0.001).
In the hierarchical composite endpoint analysis, semaglutide produced more hits than placebo (ratio, 1.72; 95% CI, 1.37 to 2.15; P < 0.001).
The mean percent change in CRP level was –43.5% with semaglutide and –7.3% with placebo (estimated treatment ratio, 0.61; 95% CI, 0.51 to 0.72; P <0.
Serious adverse events were reported in 35 participants (13.3%) in the semaglutide group and 71 (26.7%) in the placebo group.
Conclusions In patients with heart failure with preserved ejection fraction and obesity, treatment with semaglutide (2.4 mg) produced greater reductions in symptoms and physical limitations, greater improvements in exercise function, and greater weight loss than placebo. |
(Funded by Novo Nordisk; STEP-HFpEF ClinicalTrials.gov number, NCT04788511.
