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Objective: We investigated the long-term cardiovascular outcomes associated with direct oral anticoagulants (DOACs), antiplatelets and No-Treatment compared to warfarin beyond 90-days after atrial fibrillation (AF) catheter ablation.

Methods: We identified 12,010 AF patients undergoing first-time ablation in Denmark (2002-2018) and analyzed stroke, serious bleeding, cardiovascular death and the composite of these three endpoints (MACE) by incidence rates (IR) per 1000 person-years and Cox proportional-hazard models.

Results: The median age was 62 years (interquartile range [IQR]: 54-68 years); 28.8% were female, 7225 (60.2%) patients were younger than 65-years, and 6927 (57.7%) patients had CHA₂DS₂-VASc score≥2. Over a total of 65,990 person-years follow-up commencing 90-days after first-time ablation, warfarin, DOACs, antiplatelets and ‘No-treatment’ exposures covered 30,877 (46.8%), 9,452 (14.3%), 6,003 (9.1%) and 19,657 (29.8%) person-years, respectively. There was no difference between DOACs vs warfarin (HR 1.04 [0.77-1.42]_95%CI) while antiplatelets (HR 1.50 [1.11-2.05]_95%CI) and No-Treatment (HR 1.50 [1.15-1.94]_95%CI) were associated with a significantly higher rate of stroke. DOACs (HR 0.70 [0.54-0.92]_95%CI), antiplatelets (HR 0.58 [0.41-0.82]_95%CI) and No-Treatment (HR 0.52 [0.39-0.69]_95%CI) were associated with a significantly lower rate of serious bleeding compared with warfarin. We found no difference between DOACs and warfarin (HR 0.87 [0.61-1.25]_95%CI) while Antiplatelets (HR 1.42 [1.04-1.94]_95%CI) and No-treatment (HR 2.77 [2.16-3.56]_95%CI) were associated with a significantly higher rate of cardiovascular death. We observed no difference with DOACs (HR 0.86 [0.70-1.05]_95%CI), antiplatelets (HR 1.04 [0.84-1.27]_95%CI) or No-Treatment (HR 1.10 [0.93-1.31]]_95%CI) compared to warfarin in multivariable analyses regarding the composite endpoint of MACE.

Conclusions: Our study indicates a better bleeding risk profile associated with DOACs than warfarin in patients undergoing AF ablation, but no difference for the endpoints of stroke, cardiovascular death, or the composite endpoint of MACE. Despite the favourable bleeding risk, antiplatelets and No-Treatment compared with warfarin appear hazardous due to a higher rate of stroke and cardiovascular death.