SELECT: Semaglutide's CV Benefit Extends to Heart Failure Patients

John Deanfield, BChir
Credit: University College London

A subgroup analysis of the landmark SELECT trial has confirmed the benefit of semaglutide 2.4 mg among patients with heart failure across the spectrum of ejection fraction.

Using data from 4286 patients within the trial with heart failure with reduced ejection (HFrEF) or heart failure preserved ejection fraction (HFpEF), results indicate use of semaglutide 2.4 mg was associated with improved outcomes for the major adverse cardiovascular events (MACE) and a composite heart failure endpoint, regardless of ejection fraction.¹

“Our previous SELECT analysis showed the benefits of semaglutide for people with cardiovascular disease who had obesity or were overweight. This new study finds that, within this group, people with heart failure did just as well as people without in terms of the outcomes we measured," said lead investigator John Deanfield, professor of Cardiology at University College London.²

Presented at the American Heart Association’s 2023 Scientific Sessions and simultaneously published in the New England Journal of Medicine, SELECT assessed the efficacy and safety of semaglutide 2.4 mg relative to placebo therapy among patients with overweight/obesity and established cardiovascular disease but without diabetes. The trial included more than 16,000 patients and concluded use of semaglutide was associated with a 20% reduction in risk of major adverse cardiovascular events relative to placebo therapy among this cohort.¹

These data were used as the basis of a historic label expansion for the agent in March 2024 for reducing cardiovascular risk among patients with overweight or obesity with a history of cardiovascular disease. While the results received applause and acclaim from across the medical community, the interest for many quickly turned to forthcoming prespecified and subgroup analyses, including among those with heart failure.¹

In the current analysis, Deanfield and colleagues sought to assess the effects of semaglutide relative to placebo among subgroups of patients with and without a history of heart failure at enrollment, with these groups further stratified as HFpEF, HFrEF, or unclassified heart failure. The primary outcomes of interest were risk of MACE composite consisting of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, a composite heart failure outcome of cardiovascular death and hospitalization or urgent hospital visit for heart failure, cardiovascular death, and all-cause mortality.¹

Of the 17,604 individuals included in the SELECT trial, 4286 had heart failure at enrollment. Of these, 53% had HFpEF, 31.4% had HFrEF, and the remaining 15.5% had unclassified heart failure. Initial analysis revealed baseline characteristics were similar among those with and without heart failure in the trial, but patients with heart failure had a greater incidence of clinical events.¹

Primary outcome analyses indicated use of semaglutide was associated with an improvement in all outcome measures among patients with heart failure, with relative risk reductions of 28% for MACE (hazard ratio [HR] 0.72, 95% CI, 0.60 to 0.87), 21% for the heart failure composite endpoint (HR, 0.79; 95% CI,0.64 to 0.98), 24% for cardiovascular death (HR, 0.76; 95% CI, 0.59 to 0.97) for cardiovascular death; and (HR, 0.81; 95% CI, 0.66 to 1.00) for all-cause mortality compared to placebo therapy (all P-interaction >.19).¹

Semaglutide’s Effect in HFrEF (vs Placebo)

• MACE: HR, 0.65; 95% CI, 0.49 to 0.87

• Heart Failure Composite: HR, 0.79; 95% CI, 0.58 to 1.08

Semaglutide’s Effect in HFpEF (vs Placebo)

• MACE: HR, 0.69; 95% CI, 0.51 to 0.91
• Heart Failure Composite: HR, 0.75; 95% CI, 0.52 to 1.07

“This is important as there were concerns that semaglutide might be harmful for people with a type of heart failure known as reduced ejection fraction, where the heart pumps less blood around the body. Our findings show that the benefit of semaglutide was similar regardless of heart failure type,” Deanfield added.²

Investigators highlighted further analyses demonstrating there were no significant differences in benefits of semaglutide for the MACE and heart failure composite based on baseline age, sex, BMI, New York Heart Association status, and diuretic use. Investigators also highlighted results indicating semaglutide use was associated with a reduction in serious adverse events relative to placebo, regardless of heart failure subtype.¹

References:

1. Deanfield J, Verma S, Sirica BM, et al. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: A pre-specified analysis of the SELECT 2 Trial. The Lancet. Published online August 22, 2024.
2. University College London. Weight loss drug’s heart benefits extend to people with heart failure. UCL News. August 22, 2024. Accessed August 22, 2024. https://www.ucl.ac.uk/news/2024/aug/weight-loss-drugs-heart-benefits-extend-people-heart-failure.
3. Campbell P. Semaglutide (Wegovy) receives FDA label expansion to include cardiovascular risk reduction. HCP Live. March 8, 2024. Accessed August 22, 2024. https://www.hcplive.com/view/semaglutide-wegovy-receives-fda-label-expansion-to-include-cardiovascular-risk-reduction.