ESC Heart Failure 2024 - In a prespecified analysis of SELECT among CVD patients with BMI ≥27 kg/m², the efficacy and safety of semaglutide versus placebo on the rates of MACE, HF-related events, and all-cause mortality were not influenced by history of HF or HF subtype.

This summary is based on the presentation of John Deanfield, MD (London, UK) at the ESC Heart Failure Congress 2024 - Semaglutide and cardiovascular outcomes in patients with overweight or obesity and heart failure: A pre-specified analysis from the SELECT trial.

Introduction and methods

Recently, the large SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial demonstrated semaglutide reduced the risk of MACE by 20% in patients with CVD and overweight or obesity compared with placebo. In a prespecified analysis of this trial, the efficacy and safety of semaglutide were compared in patients with and with no HF.

SELECT trial was a multicenter, double-blind, placebo-controlled, event-driven, superiority, phase 3 RCT in which 17,604 patients aged ≥45 years with preexisting CVD and BMI ≥27 kg/m² but no diabetes were randomized to subcutaneous semaglutide 2.4 mg once weekly or placebo. Mean ± SD follow-up time was 39.8 ± 9.4 months.

The endpoints of the current analysis were the time to first MACE (a composite outcome of CV death, nonfatal MI, or nonfatal stroke), a composite HF outcome (HF hospitalization, urgent HF visit, or CV death), CV death, and all-cause mortality.

Main results

• The treatment effect of semaglutide versus placebo on the incidence of MACE did not differ between patients with HF at baseline (n=4286; HR: 0.72; 95%CI: 0.60–0.87) and patients with no HF (n=13,314; HR: 0.84; 95%CI: 0.74–0.97; P for interaction=0.1934).
• When HF patients were stratified by HF subtype, there was also no difference in semaglutide’s effect on MACE compared with placebo: The HR was 0.65 (95%CI: 0.49–0.87) for HFrEF patients (n=1347) and 0.69 (95%CI: 0.51–0.91) for HFpEF patients (n=2273) (P for interaction=0.8150).
• Baseline HF status did not influence semaglutide’s effect on the incidence of the composite HF outcome (HR for HF: 0.79; 95%CI: 0.64–0.98 vs. HR for non-HF: 0.85; 95%CI: 0.68–1.06; P for interaction=0.6383), nor did HF subtype (HR for HFrEF: 0.79; 95%CI: 0.58–1.08 vs. HR for HFpEF: 0.75; 95%CI: 0.52–1.07; P for interaction=0.7949).
• Additionally, the rate of all-cause mortality was not affected by baseline HF status (HR for HF: 0.81; 95%CI: 0.66–1.00 vs. HR for non-HF: 0.81; 95%CI: 0.67–0.97; P for interaction=0.9797) or HF subtype (HR for HFrEF: 0.72; 95%CI: 0.53–0.99 vs. HR for HFpEF: 0.83; 95%CI: 0.59–1.16; P for interaction=0.5596).
• For MACE, the efficacy of semaglutide versus placebo in patients with HF, HFpEF, and HFrEF was consistent across subgroups stratified by sex, age, or baseline characteristics such as BMI, HbA1c level, and NYHA class.
• The safety profile of semaglutide, including frequencies of serious adverse events and adverse events leading to permanent discontinuation of the study drug, was similar in patients with and with no HF and between HF subtypes.

Conclusion

In this prespecified analysis of the SELECT trial among CVD patients with overweight or obesity but no diabetes, the effects of semaglutide versus placebo on the rates of MACE, HF-related events, and all-cause mortality were not influenced by baseline HF status or HF subtype. Prof. Deanfield concluded that the “efficacy data combined with a reassuring safety profile support the use of semaglutide to improve CV outcomes in a broad population of patients with ASCVD and overweight or obesity irrespective of a history of any type of HF.”

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