GLP-1RA reduced the composite of cardiovascular mortality and worsening heart failure exacerbation compared to placebo (RR 0.64; 95% CI 0.45-0.92).
Meta-Analysis (n=4,474)
Does GLP-1RA reduce the composite event of cardiovascular mortality and worsening HF exacerbation in patients with heart failure and mildly reduced or preserved ejection fraction?
In patients with HFpEF or HFmrEF, GLP-1RA therapy significantly reduces heart failure exacerbations and improves functional status and body weight, though it does not significantly reduce cardiovascular mortality.
Effect estimate: RR 0.64 (95% CI 0.45-0.92)
Absolute Event Rate: 6.1% vs 8.8%
INTRODUCTION: Currently, limited guideline-directed medical therapies are available for heart failure (HF) with preserved and mildly reduced ejection fraction (EF). Both are associated with an increased risk of hospitalization and death, especially in overweight, obese, or diabetic individuals. METHODS: We searched Cochrane, Embase, and MEDLINE from inception to November 2024. Trials with HF patients randomized for GLP-1RA (glucagon-like peptide-1 receptor agonists) and reported adverse cardiovascular and mortality outcomes were included. Statistical analysis was performed using Cochrane Review Manager 5.4.1. RESULTS: 4474 patients with HF (preserved and mildly reduced EF) were included in the study. 2278 (50.91 %) received a GLP-1RA either semaglutide (1914, 84 %) or Tirzepatide (364, 16 %), and 2196 (49.01 %) received a placebo. GLP-1RA reduced the composite event of cardiovascular mortality and worsening HF exacerbation 139 vs. 194, RR: 0.64 (95 % CI: 0.45-0.92). However, on subgroup analysis, there was no significant difference in cardiovascular (CV) deaths 67 vs. 71, RR 0.89 (95 % CI: 0.65-1.24). The HF exacerbations were significantly reduced in the GLP-1RA group 83 vs. 138, RR 0.59 (95 % CI: 0.45-0.76). Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) was favorable for GLP-1RA Std Mean Difference (SMD): 7.38 (95 % CI: 5.51-9.26), reflected by an increase in 6-min walk distance in GLP-1RA groups SMD: 17.69 (95 % CI: 11.87-23.34) and contributed by a decrease in body weight in GLP-1RA groups SMD -9.56 (95 % CI -12.74 to -6.39). CONCLUSION: GLP-1RA reduce HF exacerbations and can play a role in reducing hospitalizations, improving patient's functional status, and significantly impacting the global healthcare burden of HF. However, the current data does not indicate any overall mortality benefit.
Duhan et al. (Sat,) conducted a meta-analysis in Heart failure with preserved and mildly reduced ejection fraction (n=4,474). GLP-1RA vs. Placebo was evaluated on Composite event of cardiovascular mortality and worsening HF exacerbation (RR 0.64, 95% CI 0.45-0.92). GLP-1RA reduced the composite of cardiovascular mortality and worsening heart failure exacerbation compared to placebo (RR 0.64; 95% CI 0.45-0.92).