Abstract 4364820: Impact of GLP-1 Agonists on Cardiovascular Outcomes in Patients with Heart failure with Preserved Ejection Fraction: Analysis of Real-world studies

Background: Patients with heart failure with preserved ejection fraction (HFpEF) have an increased risk of cardiovascular events. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as transformative agents in management of obesity and Type 2 diabetes mellitus(T2DM), however their effects on heart failure with preserved fraction patients remain uncertain. This study aims to investigate association between GLP-1RA therapy and cardiovascular outcomes in HFpEF patients. Methods: This retrospective cohort study utilized data from the TrinetX database encompassing adult patients diagnosed with HFpEF with T2DM or Obesity between January 2009 and January 2023.Data was extracted from electronic health records and was divided into cohorts. Cohort 1 consisted of patients with HFpEF and T2DM or Obesity treated with GLP-1RA for at least 1 year and cohort 2 included patients with HFpEF and T2DM or Obesity without GLP-1RA. Propensity score matching (PSM) analysis was used to compare cohort 1 and cohort 2 patients.After PSM, the study included 19342 patients in each cohort, predominantly white female with mean age of 65.8years in the GLP-1 RA and 72.4 years in the non-GLP -1RA group. There were similar demographic and clinical characteristics between the cohorts. Results: The analysis showed significantly reduced odds of composite primary outcome of 3-point major adverse cardiovascular events (MACE) (HR 0.378 ,95% CI 0.351-0.408 p<0.001) and all-cause mortality (HR:0.298, 95% CI:0.275-0.322, p<0.001) .Furthermore, GLP-1RA therapy was associated with significantly lower odds of hospitalization (HR:0.470, 95% CI:0.455-0.486, p<0.001) ,lower odds of furosemide dose escalation (HR:0.294, 95% CI : 0.268-0.323, p< 0.001). Kaplan-Meier survival analysis demonstrated a significantly higher incidence-free probability for the composite primary outcome in the GLP-1 RA group (91.3% vs 79.18%, X 2 = 49.792 p < 0.001) Conclusions: This study suggests that GLP-1RA therapy may confer cardiovascular benefits, including a reduction in 3-point MACE, hospitalization rates and decreased furosemide dose escalation in HFpEF patients. These findings also support the pre-existing knowledge regarding cardiovascular benefits conferred by GLP-1 agonists. Further randomized controlled trials are needed to validate these findings especially in HFpEF patients.