Efficacy of GLP-1 Receptor Agonists in Patients with Heart Failure and Mildly Reduced or Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.

Abstract

Background: Heart failure with mildly reduced or preserved ejection fraction (HFpEF) accounts for over half of heart failure cases, with obesity playing a key role. Residual risk remains high despite available therapies. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown potential cardiometabolic benefits, but their role in HFpEF remains unclear.

Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating GLP-1RAs in HFpEF was conducted. Studies evaluating GLP-1RA in combination with glucose-dependent insulinotropic polypeptide (GIP) were also included. The analyzed outcomes included cardiovascular (CV) death, worsening heart failure (HF) events, and their composite. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a random-effects model.

Results: Six RCTs with 8,788 patients were included. GLP-1RAs significantly reduced the composite outcome of CV death or worsening HF events (HR: 0.68 [0.51-0.89], p = 0.006, I² = 47%) as well as worsening HF events alone (HR: 0.56 [0.38-0.82], p = 0.003, I² = 51%). No significant reduction was observed for CV death alone (HR: 0.86 [0.67-1.12], p = 0.27, I² = 0%).

Conclusion: GLP-1RAs reduce worsening HF events and the composite of CV death or worsening HF in HFpEF, particularly in patients with obesity or diabetes. These findings support their role as a promising therapy requiring further HFpEF-focused trials.