Semaglutide treatment benefits patients with heart failure and obesity: STEP-HFpEF trial

The findings were presented at the European Society of Cardiology Congress, Amsterdam, Netherlands, on August 25, 2023, and subsequently published in the New England Journal of Medicine.

There is an increase in the prevalence of HFpEF which is associated with functional impairment and a high symptom burden, especially in patients with obesity. No therapies have been approved to target obesity-related HFpEF.

Mikhail N. Kosiborod, Saint Luke’s Mid-America Heart Institute, Kansas City, MO, and colleagues conducted a trial to compare the efficacy and safety of semaglutide among patients with heart failure with preserved ejection fraction and obesity.

The study included 529 patients who had heart failure with preserved ejection fraction and a BMI (body mass index) of 30 or higher. They were randomly assigned in a ratio of 1:1 to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks.

The primary endpoints were the change in the KCCQ-CSS (Kansas City Cardiomyopathy Questionnaire clinical summary score; scores with scores ranging from 0 to 100, higher scores suggesting fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary endpoints were the change in the 6-minute walk distance; a hierarchical composite endpoint including heart failure events, death, and differences in the change in the 6-minute walk distance and KCCQ-CSS; and change in the level of CRP (C-reactive protein).

The authors reported the following findings:

• The mean change in the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points), and the mean percentage change in body weight was −13.3% with semaglutide and −2.6% with placebo (estimated difference, −10.7 percentage points).
• The mean change in the 6-minute walk distance was 21.5 m with semaglutide and 1.2 m with placebo (estimated difference, 20.3 m).
• In the analysis of the hierarchical composite endpoint, semaglutide produced more wins than placebo (win ratio, 1.72).
• The mean percentage change in the CRP level was –43.5% with semaglutide and –7.3% with placebo (estimated treatment ratio, 0.61).
• Serious adverse events were reported in 13.3% of the participants in the semaglutide group and 26.7% in the placebo group.

"Our trial findings showed that among obese patients with HFpEF, once-weekly subcutaneous semaglutide was superior to placebo in improving patient-oriented quality of life outcomes and body weight at 52 weeks," the researchers wrote.

The limitation of the trial was that very few patients were on SGLT2 inhibitors at baseline. Also, there was no clarity on whether the improvements in HF-related QoL measures were driven by weight loss (implying that other measures of weight loss could be of potential benefit) or independent of this.

Reference: