GLP-1 receptor agonist use and clinical outcomes after atrial fibrillation ablation: a 110-center real-world analysis

Background Atrial fibrillation (AF) recurrence after catheter ablation remains common. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve cardiometabolic profiles, but their impact on post-ablation AF recurrence is unclear. Purpose To evaluate the association between GLP-1 RA therapy and AF recurrence and cardiovascular outcomes after AF ablation. Methods We performed a retrospective cohort study using the TriNetX federated database from its inception through February 28, 2026. Adults (18–80 years) undergoing AF ablation were stratified by GLP-1 RA exposure. The primary outcome was recurrent AF/atrial flutter. Secondary outcomes included repeat ablation, stroke/TIA, and heart failure (HF) hospitalization. Propensity score matching (1:1) was performed. Kaplan–Meier analysis and Cox proportional hazards models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) at 1 and 3 years. Results After 1:1 propensity score matching, 1,011 patients per group were included in the 1-year analysis and 1,239 per group in the 3-year analysis. Follow-up duration was balanced between groups. At 1 year, recurrent AF/atrial flutter occurred in 92.1% of GLP-1 users versus 94.1% of non–GLP-1 patients. Kaplan–Meier estimated event rates were 2.63% versus 2.20% (log-rank p<0.001). GLP-1 therapy was associated with a lower hazard of recurrent AF (HR 0.83, 95% CI 0.76–0.91, p=0.049). There were no significant differences in repeat ablation (HR 0.83, p=0.911), stroke/TIA (HR 1.18, p=0.451), or HF hospitalization (HR 0.98, p=0.890). At 3 years, recurrent AF occurred in 92.4% of GLP-1 users versus 94.0% of controls, with Kaplan–Meier event rates of 1.47% versus 0.62% (log-rank p<0.001). GLP-1 use remained associated with reduced AF recurrence (HR 0.76, 95% CI 0.70–0.82, p=0.016). HF hospitalization occurred in 16.4% of GLP-1 users versus 19.5% of controls. Risk analysis demonstrated a significant reduction in HF hospitalization at 3 years (OR 0.81, 95% CI 0.66–0.99, p=0.041), although the Cox model did not reach statistical significance (HR 0.86, 95% CI 0.71–1.04, p=0.433). Repeat ablation and stroke/TIA were not significantly different between groups. (Table 1, Figure 1) Conclusion In this large real-world, propensity-matched analysis, GLP-1 RA therapy was independently associated with significantly lower AF recurrence after catheter ablation, with sustained benefit through 3 years. A signal toward reduced HF hospitalization was also observed. These findings suggest a possible novel arrhythmia-protective effect of GLP-1 therapy beyond glycemic control and support further prospective evaluation of GLP-1 agents as adjunctive therapy in AF management.