The effect of glucagon-like peptide-1 receptor agonists on patients with heart failure with reduced ejection fraction – a large cohort analysis

Background: Evidence on glucagon-like peptide-1 receptor agonists (GLP-1 RA) in patients with heart failure with reduced ejection fraction (HFrEF) remains limited and conflicting.

Purpose: To examine the safety and efficacy of GLP1 RA therapy in patients with HFrEF using a large national database.

Methods: This observational retrospective cohort study analyzed data from Clalit Health Services` electronic medical records (2014-2023). Using 1:1 matching by age, sex, and clinical characteristics, HFrEF patients treated with GLP-1 RA were compared to those without such treatment. Primary outcomes were heart failure (HF) hospitalization and death.

Results: From 22,927 HFrEF patients, 4,186 were matched and included (2,093 per group). The cohort`s mean age was 69, with 30% female participants and a mean BMI of 30.8. Most patients received guideline-directed medical therapy, though sodium-glucose cotransporter 2 inhibitor use was low. The median follow-up was 30 months.

In multivariable analysis, GLP-1 RA treatment was associated with lower mortality (HR 0.45, 0.40-0.52, p<0.001) and reduced HF hospitalization (HR 0.62, 0.54-0.72, p<0.001). Factors associated with better outcomes included higher glomerular filtration rate, younger age, lower BMI, and treatment with ACE inhibitors/Angiotensin receptor blockers or beta-blockers. Chronic pulmonary disease, peripheral vascular disease, and insulin treatment were associated with worse outcomes.

Conclusion: In this large cohort of HFrEF patients, GLP-1 RA therapy combined with guideline-directed medical therapy was associated with reduced mortality and HF hospitalization. Further studies with larger cohorts are needed to confirm these findings.