Comparative Effectiveness of Glucagon-like Peptide-1- Receptor Agonists in Patients With Heart Failure With Preserved or Minimally Reduced Ejection Fraction: A Comprehensive Bayesian Network Meta-Analysis and Network Meta-Regression.

OBJECTIVES: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown beneficial effects on clinical outcomes in patients with heart failure (HF) with preserved ejection fraction (HFpEF) or minimally reduced ejection fraction (HFmrEF). This network meta-analysis (NMA) aimed to consolidate evidence from RCTs assessing the effects of GLP-1 RAs in HFpEF and HF with reduced ejection fraction. METHODS: Several databases were searched comprehensively for relevant RCTs. A Bayesian NMA was conducted using R, and meta-regression was employed to investigate potential sources of heterogeneity. Statistical significance was evaluated using 95% credible intervals (CrIs) and surface under the cumulative ranking curve to rank treatment effectiveness. The primary outcome was hospitalization for HF (HHF). RESULTS: Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included. Compared to placebo, semaglutide reduced the risk of HHF (HR 0.52, 95% CrI [0.25, 0.87]), while tirzepatide (HR 0.51, 95% CrI [0.16, 1.24]) and exenatide (HR 0.82, 95% CrI [0.33, 1.73]) demonstrated no effect. Semaglutide and exenatide, but not tirzepatide, reduced the risk of all-cause mortality. None affected cardiovascular mortality. Semaglutide decreased the risk of worsening of HF events; tirzepatide did not. Tirzepatide and semaglutide enabled weight loss; however, only semaglutide notably enhanced the 6-minute walk distance. According to the surface under the cumulative ranking curve values, tirzepatide ranked highest for reducing HHF and body weight, semaglutide for decreasing cardiovascular mortality and worsening of HF events and improving the 6-minute walk distance, and exenatide for reducing all-cause mortality. CONCLUSION: GLP-1 RAs provide significant benefits for patients with HFpEF or HFmrEF, with semaglutide offering more advantages than tirzepatide and exenatide.