The Effect of Glucagon-Like Peptide-1 Receptor Agonists versus Sodium-Glucose Cotransporter-2 Inhibitors Alone and in Combination on AF Recurrence and Cardiovascular Outcomes after Catheter Ablation for Atrial Fibrillation.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes, but their effect on atrial fibrillation (AF) recurrence after catheter ablation (CA) for AF remains undefined. OBJECTIVE: To evaluate the impact of GLP-1 RA, SGLT2i, and their combination on AF recurrence following catheter ablation. METHODS: Using the TriNetX database (2018-2024), adults with AF who underwent CA for AF were grouped by GLP-1 RA, SGLT2i, or combination use within 12 months prior to CA. The primary outcome was AF recurrence, defined as repeat CA, cardioversion, or antiarrhythmic drug use after a 3-month blanking period. Propensity score matching (PSM) was applied for GLP-1 RA vs SGLT2i, combination vs GLP-1 RA, and combination vs SGLT2i. RESULTS: In GLP-1 RA vs SGLT2i (n=1,393 each), AF recurrence was similar (HR 1.01, 95% CI 0.89-1.15; p=0.86). In combination vs GLP-1 RA (n=952 each), recurrence was similar (HR 1.13, 95% CI 0.98-1.31; p=0.10), but all-cause mortality was lower (HR 0.54, 95% CI 0.34-0.87; p=0.01) in the combination group. In combination vs SGLT2i (n=1,213 each), recurrence was similar (HR 1.09, 95% CI 0.96-1.24; p=0.20), while all-cause mortality was reduced (HR 0.60, 95% CI 0.39-0.93; p=0.02). Secondary outcomes, including stroke, heart failure, and all-cause hospitalization, were similar among all three groups. CONCLUSION: GLP-1 RA and SGLT2i alone or in combination were associated with comparable AF recurrence rates following CA for AF. However, combination therapy was consistently associated with lower all-cause mortality.