BACKGROUND: Heart failure (HF) with mildly reduced or preserved ejection fraction (HFpEF) accounts for over half of cases of HF, 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 evaluating GLP-1RAs in HFpEF were conducted. Studies evaluating GLP-1RA in combination with glucose-dependent insulinotropic polypeptide (GIP) were also included. The analyzed outcomes included cardiovascular (CV) death, worsening HF events and their composite. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled by using a random-effects model.
RESULTS: Six randomized controlled trials involving 8788 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.
