Comparative cardiovascular outcomes of semaglutide versus tirzepatide in patients with atrial fibrillation undergoing catheter ablation: a retrospective cohort study

Background GLP-1 receptor agonists have demonstrated cardiovascular benefits in patients with obesity and type 2 diabetes. However, comparative data on outcomes following atrial fibrillation (AF) ablation between different GLP-1 receptor agonists remain limited. Objective To compare cardiovascular outcomes between semaglutide and tirzepatide in patients with AF and obesity or diabetes who underwent catheter ablation. Methods This retrospective cohort study utilized the TriNetX US Collaborative Network (68 healthcare organizations). Adults (≥18 years) with AF and either diabetes mellitus or obesity who underwent AF catheter ablation while receiving semaglutide (n=1,861) or tirzepatide (n=860) were identified. Exclusion criteria included type 1 diabetes, end-stage renal disease, dialysis dependence, malignancy, pregnancy, heart transplant, heart assist device, and hyperthyroidism. Propensity score matching (1:1) balanced cohorts for demographics, comorbidities, medications, and laboratory values, yielding 842 matched pairs. Outcomes assessed over 3 years included repeat ablation, stroke, acute myocardial infarction (MI), events of heart failure, cardioversion, and ventricular tachycardia (VT). Results After propensity score matching, mean age was 63 years (65% male) in both cohorts. Semaglutide use was associated with significantly higher rates of repeat ablation (7.2% vs. 4.2%; RR 1.74, 95% CI 1.16-2.61; p<0.005), heart failure events (31.7% vs. 25.3%; RR 1.25, 95% CI 1.08-1.46; p<0.005), cardioversion (9.4% vs. 6.4%; RR 1.46, 95% CI 1.05-2.04; p<0.005), and ventricular tachycardia (5.9% vs. 2.7%; RR 2.17, 95% CI 1.34-3.53; p<0.005). No significant differences were observed in stroke (3.6% vs. 2.5%; RR 1.43, 95% CI 0.83-2.48) and acute MI (3.6% vs. 3.1%; RR 1.15, 95% CI 0.69-1.93). Conclusions In propensity score-matched patients with AF undergoing catheter ablation, semaglutide was associated with higher rates of repeat ablation, heart failure, cardioversion, and ventricular tachycardia compared to tirzepatide. No significant differences were observed in stroke or acute MI. These findings warrant further investigation in prospective studies to determine optimal GLP-1 receptor agonist selection in the post-AF ablation population.