Association between comorbidity burden and outcomes of catheter ablation vs. medical therapy for atrial fibrillation: insights from the CABANA trial

Abstract

AIMS: Multimorbidity frequently coexists with atrial fibrillation (AF) and complicates treatment decisions. While current guidelines offer selective recommendations for catheter ablation in this group, evidence remains limited. This study aimed to evaluate whether comorbidity burden modifies the effectiveness of catheter ablation vs. antiarrhythmic drug therapy. METHODS AND RESULTS: In this post hoc analysis of the CABANA trial, patients were stratified by overall comorbidity burden using a data-driven threshold based on the distribution of 15 pre-specified conditions. The primary outcome was a composite of all-cause mortality, disabling stroke, serious bleeding, or cardiac arrest. Secondary outcomes included cardiovascular hospitalization and a composite of all-cause mortality or cardiovascular hospitalization. Additional outcomes included AF recurrence and AF-related quality of life in a sub-cohort. Of 2204 patients, 736 had high comorbidity burden {?4 conditions, based on a data-driven threshold; median age 68.0 [interquartile range (IQR): 63.0-73.0], 67.1% male} and 1468 had low burden [median age 67.0 (IQR: 61.0-71.0), 60.7% male]. Over a median follow-up of 3.9 years (IQR: 2.4-5.1), for the primary outcome, the adjusted hazard ratio for catheter ablation vs. drug therapy was 0.62 [95% confidence interval (CI): 0.42-0.93] in patients with high comorbidity burden and 1.16 (95% CI: 0.76-1.77) in those with low burden (interaction P = 0.038). Secondary outcomes also tended to favour ablation in the high comorbidity burden group. Moreover, catheter ablation significantly reduced AF recurrence, with relative risk reductions of 49% and 40% in the low- and high-burden groups, respectively. Furthermore, catheter ablation improved AF-related quality of life in both comorbidity groups, with more sustained and pronounced benefits over time in patients with high comorbidity burden. CONCLUSION: Catheter ablation was associated with more favourable clinical outcomes in AF patients with high comorbidity burden, which support broader consideration of ablation in this population, though prospective trials are needed to confirm and guide clinical decision-making in personalized rhythm management. PRE-REGISTERED CLINICAL TRIAL NUMBER: NCT00911508.