Log in to MyACC
Semaglutide in HFpEF: Pooled Analysis of Four Randomized Trials
Quick Takes
- In a post hoc pooled analysis of four randomized trials enrolling HFpEF patients and comparing semaglutide to placebo, semaglutide was associated with reduced risk for a composite of CV death and worsening HF.
- Benefit of semaglutide was more pronounced among individuals with obesity compared to nonobese patients.
- Semaglutide was associated with a higher incidence of GI and hepatobiliary side effects but serious adverse events leading to permanent drug discontinuation were higher for placebo.
Study Questions:
Does semaglutide reduce risk for adverse cardiovascular (CV) events in patients with heart failure with preserved ejection fraction (HFpEF)?
Methods:
This study pooled post hoc data from the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM trials. All these trials compared semaglutide to placebo in patients with HFpEF. The main outcome assessed was composite of time to CV death or first worsening HF event (i.e., hospitalization/urgent visits). Safety endpoints included serious adverse events leading to drug discontinuation permanently.
Results:
All four trials cumulatively enrolled 22,282 patients and 16.8% had a history of HFpEF at enrollment. Overall, 1,914 were assigned to semaglutide and 1,829 to placebo. Median age was 64 years, 38% were women, and 90% were White. Semaglutide reduced risk for CV death or worsening HF events compared to placebo with a hazard ratio (HR) of 0.69 (95% confidence interval [CI], 0.53-0.89). The number needed to treat (NNT) to prevent one CV death or worsening HF event was 97 in 1 year and 28 in 4 years. Semaglutide lowered risk for worsening HF with HR 0.59 (95% CI, 0.41-0.82) with NNT of 95 in 1 year and 30 in 4 years. Risk for CV death was no different with semaglutide (HR, 0.82; 95% CI, 0.57-1.16). Interaction effect with obesity was statistically significant. Patients on semaglutide had fewer serious adverse events compared with placebo except for hepatobiliary disorders and gastrointestinal (GI) side effects that were more common with semaglutide.
Conclusions:
In a post hoc pooled analysis of four randomized trials including HFpEF patients and comparing semaglutide to placebo, semaglutide was associated with reduced risk for a composite of CV death and worsening HF events.
Perspective:
Obesity-associated HFpEF is associated with disabling symptoms with a high risk for adverse CV events. Sodium-glucose cotransporter-2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists are available treatment options but both do not treat obesity, which is a major contributor to both disease pathophysiology as well as symptoms. There is a paucity of treatment options for obesity in HFpEF patients and hence, glucagon-like peptide-1 (GLP-1) receptor agonists hold a promising role. In this post hoc pooled analysis of four randomized trials, semaglutide reduced risk for a composite endpoint of CV death and worsening HF—similar to SGLT2 inhibitors. However, the drug did not decrease risk for CV death alone. More importantly, drug effects were pronounced in patients with body mass index >35 kg/m2 and it was well tolerated. These data suggest that semaglutide should be considered in patients with HFpEF and obesity.
Clinical Topics: Heart Failure and Cardiomyopathies, Novel Agents, Prevention
Keywords: GLP-1 Receptor, Heart Failure, Preserved Ejection Fraction, Obesity
< Back to Listings
