Impact of GLP-1 receptor agonists on cardiovascular outcomes in heart failure with preserved ejection fraction (HFpEF): systematic review and meta-analysis

Abstract

Background: Pharmacologic therapies for heart failure with preserved ejection fraction (HFpEF) have shown limited efficacy, and the impact of GLP-1 receptor agonists (GLP-1 RAs) remains unclear. This meta-analysis evaluates their effects on mortality and hospitalization in HFpEF.

Methods: We obtained the data from PubMed, Scopus, Embase, and Web of Science for all eligible studies, including clinical trials (RCT) and cohorts comparing GLP-1 RAs to placebo or other hypoglycemic agents in patients with HFpEF published until December 31st, 2024. The Grade and Risk of Bias (ROB) tool assessment was used to evaluate the quality of the evidence. Data on the primary outcome, the composite of all-cause mortality and HF-related hospitalization, was pooled using a random effect meta-analysis with additional subgroup analyses. Risk ratios (RR), hazard ratios (HR), or mean differences with 95% confidence intervals (CI) are presented accordingly.

Results: Six studies (five RCTs, one cohort) including 4043 patients were analyzed. Five studies evaluated semaglutide and one tirzepatide. GLP-1 RAs reduced the composite outcome of all-cause mortality and HF hospitalization by 27% (HR 0.73; 95% CI: 0.60-0.90; I² = 0%). Subgroup analyses revealed greater benefits in patients with atrial fibrillation. GLP-1 RAs also reduced HF hospitalizations alone (HR 0.57; 95% CI: 0.32-1.00), though no significant effect was found on all-cause mortality (HR 0.81; 95% CI: 0.58-1.14). RCTs showed a low risk of bias.

Conclusion: GLP-1 RAs may significantly lower the combined risk of mortality and hospitalization in patients with HFpEF.

Keywords: GLP-1 receptor antagonist; Heart failure with preserved ejection fraction; Hospitalization; Meta-analysis; Mortality; Semaglutide; Tirzepatide.