Abstract Body (Do not enter title and authors here): Background
Glucagon-like peptide-1 (GLP-1) receptor agonists are well-established glucose-lowering medications for the treatment of type 2 diabetes, and are cardio-protective by reducing the incidence of major adverse cardiovascular events (MACE). However, there is limited data available with conflicting results on safety of GLP-1RAs among patients with heart failure (HF) with chronic kidney disease (CKD) patients.
Objective
To assess the potential therapeutic benefits of GLP-1RAs in HF patients with CKD.

Method
We queried the TriNetX Global Collaborative Network for adult’s patients with heart failure and chronic kidney disease (CKD) from January 2005 to April 2023, and created two cohorts: one with heart failure and CKD on GLP-1 RAs and the other one heart failure and CKD on placebo as control cohort. Both the cohorts were followed for 12 months. We used the ICD-10-CM codes to identify comorbidities, and RxNorm for prescription. Demographics and laboratory values were reported by TriNetX. Propensity score matched analysis (PSM) was done for age, gender, race, hypertension, diabetes mellitus, chronic kidney disease, smoking status, hemoglobin level, LDL level, left ventricular ejection fraction and various drugs including ACEi, ARBi, beta blockers, aldosterone receptor antagonists, SGLT-2 inhibitors and statins. Primary outcome was all-cause mortality (ACM) while secondary outcomes were acute myocardial infarction (AMI), major adverse cardiovascular outcome (MACE) (Composite of ACM, AMI, and ischemic stroke), hemorrhagic stroke, and ischemic stroke.

Results
Amongst the 1,05,414 patients (52, 707 patients in each group), the mean age of patients were 68.8 and 68.0 in GLP-1 RAs and control cohort respectively. PSM analysis showed that at one year of follow-up, GLP-1 RAs in heart failure with CKD patients was associated with significantly lower risk of primary outcome i.e., ACM (RR 0.400, 95% CI: 0.384-0.417) as compared with control. Heart failure with CKD patients on GLP-1 RAs were also associated with significantly reduced MACE (RR 0.536, 95% CI: 0.515-0.557), AMI (RR 0.633, 95% CI: 0.597-0.671), ischemic stroke (RR 0.760, 95% CI 0.712-0.811) and hemorrhagic stroke (RR 0.493, 95% CI 0.423-0.575) as compared with control.

Conclusion: GLP-1 RAs use among patients with HF and CKD were associated with significant reduction in MACE, ACM, and stroke.