Abstract
Background: Semaglutide, a glucagon-like peptide-1 receptor agonist, reduces the risk of major adverse cardiovascular (CV) events (MACE) in overweight/obesity, but its effects on outcome in patients with atherosclerotic CV disease (ASCVD) and heart failure (HF) are unknown.
Methods: In SELECT, semaglutide 2.4 mg weekly reduced MACE by 20% in patients with pre-existing ASCVD, and overweight/obesity (BMI 27kg/m2), without diabetes. In a pre-specified analysis, we examined the impact of semaglutide compared with placebo, in patients with and without a history of HF at enrolment, subclassified as preserved or reduced ejection fraction (HFpEF and HFrEF), or unclassified HF. Endpoints comprised MACE (composite of nonfatal myocardial infarction, nonfatal stroke, and CV death); a composite HF outcome (CV death or hospitalisation/urgent visit for HF); CV death; and all-cause death.
Findings: Of the 17,604 patients randomised, 4,286 had a history of investigator-defined HF at enrolment, (HFpEF [2,273], HFrEF [1,347], or unclassified HF [666]). Baseline characteristics were comparable between patients with and without HF. Patients with HF had a higher rate of clinical events. Semaglutide improved all outcome measures in patients with HF (hazard ratio [95% confidence interval]; 0.72 (0.60–0.87) for MACE; 0.79 (0.64–0.98) for HF composite; 0.76 (0.59–0.97) for CV death; and 0.81 (0.66–1.00) for all-cause death) to a similar degree, compared to those without HF (interaction p-values >0.19). Patients with HFrEF had higher absolute event rates than those with HFpEF. However, the benefit from semaglutide was similar in both subgroups (interaction p-values >0.26) and did not differ significantly by baseline characteristics (age, sex, BMI, glycaemic status, or NYHA class). Serious adverse events were less frequent with semaglutide versus placebo, regardless of HF subtype.
Interpretation: In patients with ASCVD and overweight/obesity, treatment with semaglutide 2.4 mg reduced MACE and composite HF endpoints compared to placebo in those with and without clinical HF, regardless of HF subtype.
Funding: Novo Nordisk A/S.
Methods: In SELECT, semaglutide 2.4 mg weekly reduced MACE by 20% in patients with pre-existing ASCVD, and overweight/obesity (BMI 27kg/m2), without diabetes. In a pre-specified analysis, we examined the impact of semaglutide compared with placebo, in patients with and without a history of HF at enrolment, subclassified as preserved or reduced ejection fraction (HFpEF and HFrEF), or unclassified HF. Endpoints comprised MACE (composite of nonfatal myocardial infarction, nonfatal stroke, and CV death); a composite HF outcome (CV death or hospitalisation/urgent visit for HF); CV death; and all-cause death.
Findings: Of the 17,604 patients randomised, 4,286 had a history of investigator-defined HF at enrolment, (HFpEF [2,273], HFrEF [1,347], or unclassified HF [666]). Baseline characteristics were comparable between patients with and without HF. Patients with HF had a higher rate of clinical events. Semaglutide improved all outcome measures in patients with HF (hazard ratio [95% confidence interval]; 0.72 (0.60–0.87) for MACE; 0.79 (0.64–0.98) for HF composite; 0.76 (0.59–0.97) for CV death; and 0.81 (0.66–1.00) for all-cause death) to a similar degree, compared to those without HF (interaction p-values >0.19). Patients with HFrEF had higher absolute event rates than those with HFpEF. However, the benefit from semaglutide was similar in both subgroups (interaction p-values >0.26) and did not differ significantly by baseline characteristics (age, sex, BMI, glycaemic status, or NYHA class). Serious adverse events were less frequent with semaglutide versus placebo, regardless of HF subtype.
Interpretation: In patients with ASCVD and overweight/obesity, treatment with semaglutide 2.4 mg reduced MACE and composite HF endpoints compared to placebo in those with and without clinical HF, regardless of HF subtype.
Funding: Novo Nordisk A/S.
| Original language | English |
|---|---|
| Pages (from-to) | 773-786 |
| Number of pages | 14 |
| Journal | The Lancet |
| Volume | 404 |
| Issue number | 10454 |
| DOIs | |
| Publication status | Published - 24 Aug 2024 |
Keywords
- Cardiovascular disease
- heart failure
- major adverse cardiovascular events
- cardiovascular mortality
- heart failure hospitalisation
- HFrEF
- HFpEF
- semaglutide
- weight loss
