Catheter Ablation vs Drug Therapy in Patients With Atrial Fibrillation and Nonmodifiable Recurrence Risk Factors: A Secondary Analysis of the CABANA Randomized Clinical Trial.

Importance: Large-scale randomized studies evaluating the impact of catheter ablation on cardiovascular prognoses across different atrial fibrillation (AF) recurrence risk profiles are lacking. Objective: To investigate the benefits of catheter ablation in patients with varying numbers of nonmodifiable recurrence risk factors (NMRRFs). Design, Setting, and Participants: This study was a post hoc subanalysis of the multinational, multicenter, open-label Catheter Ablation vs Anti-Arrhythmic Drug Therapy for Atrial Fibrillation (CABANA) randomized clinical trial, for which enrollment occurred from November 2009 to April 2016, with follow-up until December 31, 2017. Individuals with AF and at least 1 stroke risk factor were recruited in the CABANA trial. Only those with complete NMRRF data were included in this secondary analysis. Data were analyzed from November 1, 2023, to May 12, 2025. Exposure: Patients were categorized into 2 subgroups based on their number of NMRRFs (<3 or ≥3 risk factors). Main Outcomes and Measures: The primary end point of the CABANA trial was death, disabling stroke, serious bleeding, or cardiac arrest. Four NMRRFs were examined: AF duration more than 1 year, persistent or long-standing persistent AF, age older than 65 years, and female sex. Multivariable Cox proportional hazards regression models with adjustment were performed to investigate the benefit of ablation in each subgroup. Results: In total, 2185 patients (median age, 67.0 years [IQR, 62.0-72.0 years]; 1373 males [62.8%]) with complete NMRRF data were included. Of these patients, 1100 (50.3%) were randomized to receive catheter ablation and 1085 (49.7%) were randomized to receive drug therapy. Most patients (1469 [67.2%]) had fewer than 3 NMRRFs, while 716 (32.8%) had 3 or more. In patients with fewer than 3 NMRRFs, catheter ablation reduced the primary end point (adjusted hazard ratio [AHR], 0.59 [95% CI, 0.41-0.86]). However, the difference was not significant in those with 3 or more NMRRFs (AHR, 1.55 [95% CI, 0.93-2.58]). The interaction between the primary end point and the NMRRF category was significant (P for interaction = .003). Across all NMRRF groups, ablation did not reduce all-cause mortality (<3 NMRRFs: AHR, 0.65 [95% CI, 0.41-1.02] and ≥3 NMRRFs: AHR, 1.23 [95% CI, 0.66-2.33]) but decreased AF recurrence (<3 NMRRFs: AHR, 0.46 [95% CI, 0.40-0.52] and ≥3 NMRRFs: AHR, 0.58 [95% CI, 0.49-0.69]) and improved quality of life throughout follow-up for symptom frequency (<3 NMRRFs: -1.63 [95% CI, -2.18 to -1.07] and ≥3 NMRRFs: -1.15 [95% CI, -1.98 to -0.31]). Conclusions and Relevance: In this secondary analysis of the CABANA randomized clinical trial, the findings suggest that catheter ablation yielded significant cardiovascular benefits in patients with AF with fewer than 3 NMRRFs compared with drug therapy. This study lays the foundation for more personalized AF management, potentially optimizing resource allocation and influencing the direction of research and clinical practice in this field. Trial Registration: ClinicalTrials.gov Identifier: NCT00911508.