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

Feb 24, 2025Journal of cardiac failure

Effectiveness of GLP-1 Drugs in Heart Failure Patients with Mildly Reduced or Normal Heart Pumping

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Abstract

GLP-1 receptor agonists reduced the composite outcome of cardiovascular death or worsening heart failure events by 32% in patients with heart failure and preserved ejection fraction.

Six randomized controlled trials with 8788 patients were analyzed.
The use of GLP-1 receptor agonists is associated with a significant reduction in worsening heart failure events (hazard ratio: 0.56).
No significant reduction in cardiovascular death alone was observed (hazard ratio: 0.86).
The findings suggest potential benefits of GLP-1 receptor agonists in heart failure with preserved ejection fraction, especially in those with obesity or diabetes.

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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.

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

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