Semaglutide reduces clinical HF events in patients with HFpEF

This summary is based on the presentation of Mikhail Kosiborod, MD (Kansas City, MO, US) at the ESC Congress 2024 - Effects of semaglutide on clinical events in heart failure with preserved ejection fraction: a pooled, participant-level analysis of SELECT, FLOW, STEP-HFpEF and STEP-HFpEF DM trials.

Introduction and methods

HFpEF is associated with a high risk of cardiovascular mortality and worsening HF events, especially in patients with overweight and obesity. In the STEP-HFpEF program, the GLP1-RA semaglutide versus placebo improved HF-related symptoms and physical limitations, and reduced body weight in patients with obesity-related HFpEF. However, whether semaglutide reduces clinical HF events in patients with HFpEF remains unknown.

The aim of this pooled analysis of individual patient-level data from SELECT, FLOW, STEP-HFpEF and STEP-HFpEF DM was to evaluate whether semaglutide reduces the risk of clinical HF events in patients with HFpEF.

The STEP-HFpEF program enrolled 1145 participants with obesity-related HFpEF, the SELECT trial enrolled 17,604 participants with established CVD and overweight or obesity but without diabetes, and the FLOW trial enrolled 3533 participants with T2D and CKD. This analysis included all participants from STEP-HFpEF and STEP-HFpEF DM trials (n=1145), and participants with HFpEF from SELECT (n=2273) and FLOW (n=325), leading to a total cohort of 3743 patients. Participants were randomized to once-weekly subcutaneous semaglutide (2.4 mg in STEP-HFpEF, STEP-HFpEF DM, and SELECT; and 1.0 mg in FLOW; n=1914) or placebo (n=1829).

The main endpoint was a composite of cardiovascular mortality or worsening HF events (hospitalization or urgent visit due to HF). Secondary outcomes were the individual components of the main endpoint, and safety outcomes.

Main results

• Semaglutide reduced the risk of the composite outcome of cardiovascular mortality or HF events compared with placebo (HR: 0.69; 95%CI: 0.53-0.89; P=0.0045).
• Semaglutide reduced the risk of first HF events (HR: 0.59; 95%CI: 0.41-0.82; P=0.0019), whereas there was no significant effect on cardiovascular mortality (HR: 0.82; 95%CI: 0.57-1.16; P=0.25).
• The effects of semaglutide on the composite outcome and the individual components were consistent across the 4 trials.
• The beneficial effects of semaglutide on the composite of cardiovascular mortality or worsening HF was modified by BMI (HR: 0.49 for BMI >35 kg/m²; 95%CI: 0.33-0.70; and HR: 0.96 for BMI <35 kg/m²; 95%CI: 0.67-1.38; P=0.0093). Across other key patient subgroups, the effects of semaglutide were consistent.
• There was a lower incidence rate of serious adverse events in the semaglutide group compared with the placebo group (29.9% vs. 38.7%).

Conclusion

In this pooled analysis of SELECT, FLOW, STEP-HFpEF and STEP-HFpEF DM trials among patients with HFpEF, semaglutide reduced the risk of the composite outcome of cardiovascular mortality or worsening HF events. Semaglutide had a beneficial effect on worsening HF events alone, whereas its effect on cardiovascular mortality was not significant. The beneficial effect of semaglutide was attenuated in patients with lower BMI. “Collectively, these data certainly support semaglutide as an efficacious treatment option in people with heart failure and preserved ejection fraction”, says Mikhail Kosiborod.

- Our reporting is based on the information provided at the ESC Congress 2024 -

The findings of this study were simultaneously published in Lancet.