Impact of GLP-1 Receptor Agonist on Atrial Fibrillation Recurrence After Catheter Ablation in Non-Obese Patients

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been associated with reduced atrial fibrillation (AF) recurrence after catheter ablation in obese and diabetic populations, largely attributed to weight reduction. Whether these agents provide weight-independent antiarrhythmic benefits remains unclear. We evaluated the association between GLP-1 RA therapy and long-term clinical outcomes following AF ablation in non-obese patients.

We conducted a retrospective cohort study using the TriNetX U.S. Collaborative Network. Adults (≥18 years) with body mass index (BMI) ≤29.9 kg/m² who underwent AF ablation between 2010 and 2025 were identified. Patients receiving GLP-1 RAs within 6 months of ablation were compared with non-users. Propensity score matching (1:1) balanced demographics, comorbidities, medications, and laboratory variables. Outcomes were assessed at 1 and 3 years following a 3-month blanking period. Primary endpoints included atrial flutter, cardioversion, repeat ablation, and antiarrhythmic drug (AAD) use. Secondary outcomes included heart failure exacerbation, all-cause hospitalization, stroke, and mortality.

After matching, 1749 patients were included in each group (mean age 68 years; 38% female). At 1 year, GLP-1 RA use was associated with lower cardioversion (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.40-0.91), reduced AAD use (HR 0.68; 95% CI 0.61-0.77), decreased heart failure exacerbation (HR 0.53; 95% CI 0.32-0.85), and fewer hospitalizations (HR 0.69; 95% CI 0.51-0.94). Repeat ablation, stroke, and mortality were similar. At 3 years, reductions in cardioversion, AAD use, and heart failure exacerbation persisted.

In non-obese patients undergoing AF ablation, GLP-1 RA therapy was associated with reduced arrhythmia-related interventions and heart failure exacerbation, supporting potential weight-independent antiarrhythmic effects. Prospective trials are warranted.