Semaglutide and Cardiovascular Outcomes in Patients with Overweight or Obesity and Heart Failure - SELECT-HF

Published Congress: HFA 2024

Link:  https://www.nejm.org/doi/full/10.1056/NEJMoa2307563

Dr. Şeyda Dereli

Background:
Semaglutide, a GLP-1 receptor agonist, is known to reduce the risk of major adverse cardiovascular events in diabetic patients. In the SELECT study, subcutaneous administration of 2.4 mg semaglutide once a week was proven to be superior to placebo in reducing cardiovascular risk in non-diabetic overweight or obese patients.

Objective:
In this subgroup analysis, it was aimed to evaluate the cardiovascular outcomes and safety of semaglutide, its effect on major adverse cardiovascular events was previously evaluated in the SELECT study, in non-diabetic patients who are overweight or obese and also diagnosed with heart failure. The evaluation was planned to be made according to heart failure subgroups.

Methods:
Among the patients included in the SELECT study (N = 17604, mean age 61.6±8.9, 72.3% male), 4286 patients were diagnosed with heart failure. The patients were divided into two groups: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). In each group, patients administered 2.4 mg subcutaneous semaglutide once a week were compared with placebo.

Results :
A total of 2273 HFpEF patients underwent randomization, 1174 were assigned to receive semaglutide and 1099 to receive placebo; and a total of 1347 HFrEF patients were included in the study,  654 were assigned to receive semaglutide and 693 to receive placebo. During the 48-month follow-up period, a decrease in major adverse cardiovascular events and composite of the heart failure outcomes was observed in HFpEF group who treated with semaglutide (HR 0.69 ; 95% CI 0.51-0.91 , HR 0.75; 95% CI 0.52-1.07). Likewise, a decrease in major adverse cardiovascular events and composite of the heart failure outcomes was detected in HFrEF group who received semaglutide compared to placebo (HR 0.65; 95% CI 0.49-0.87 , HR 0.79 ; 95% CI 0.58-1.08). Cardiovascular death and all-cause mortality favored the group receiving semaglutide in both HF subgroups. The number of patients who experienced serious adverse cardiac events was 169 (14.4%) in the semaglutide arm and 191 (17.4%) in the placebo group in patients with HFpEF. In patients with HFrEF, 140 (21.4%) serious adverse cardiac events were recorded in the semaglutide arm compared to 186 (26.8%) in the placebo group. This study also found that semaglutide did not cause vascular, gastrointestinal, renal/urinary and hepatobiliary serious side effects compared to placebo in HF patients.

Conclusion:
The SELECT study allowed the efficacy of semaglutide to be evaluated in a very large group of heart failure patients. Weekly subcutaneous administration of semaglutide was superior to placebo in reducing major adverse cardiovascular events and cardiovascular deaths in heart failure patients. Importantly, this study demonstrated that GLP-1 receptor agonists can be used safely in HF patients.

Interpretations:
The results of this study, when examined with data from the STEP-HFpEF, LIVE and FIGHT studies, suggest that GLP-1 receptor agonists may have a role in the treatment of heart failure in the future. However, there is still a need for larger prospective randomized controlled studies to evaluate GLP-1 receptor agonists in heart failure patients.