The new era of atrial fibrillation treated by direct oral anticoagulants and catheter ablation—Comment on the “HAF‐NET Registry”

Atrial Fibrillation (AF) is a common cardiac arrhythmia, affecting an estimated 33.5 million individuals worldwide. Patients with AF have a 5‐fold greater risk of a stroke. Therefore, anticoagulant therapy is essential for managing the thrombotic risks. Although the vitamin K antagonist, warfarin, has been the only available oral anticoagulant treatment option, new direct oral anticoagulants (DOACs) that directly target thrombin or activated factor X, such as dabigatran, rivaroxaban, apixaban, and edoxaban, have undergone trials investigating their safety and efficacy in the management of thromboembolic strokes due to AF. In these clinical trials, DOACs are more effective than or at least equal to warfarin for the prevention of strokes and systemic embolisms in AF patients, and have had a lower risk of intracranial bleeding. Therefore, DOACs have been adopted in clinical practice more and more because of their practical advantages over warfarin. Catheter ablation has become the therapeutic option for AF over the last two decades. Because recent studies have suggested the advantages of catheter ablation of AF for a reduction in the AF burden, prolongation of the time to the first recurrence, improvement in the quality of life, and reduction in the all‐cause mortality and cardiovascular hospitalizations compared to antiarrhythmic drug therapy, catheter ablation of AF has also been increasing year‐by‐year. Therefore, population or community‐based registry studies in a new era that reflects the transition of the treatments of AF are desired. The HAF‐NET (HYOGO ATRIAL FIBRILLATION NETWORK) Registry is a multicenter, prospective, observational study of patients with AF that was implemented in urban areas of Japan from 2015 to 2016. Almost 30% of the enrolled patients had a history of catheter ablation. Anticoagulant drugs were used in 86% and DOACs in half of the patients with anticoagulants.1 After the release of the DOACs, two clinical multicenter registry studies on AF were studied in Japan.2,3 In the Fushimi AF Registry, where the patients were enrolled in 2011, DOACs were used in only 2.1% and catheter ablation was performed in 5.3% of the enrolled patients. In the SAKURA AF Registry, which started in 2013 and ceased in 2015, DOACs were used in 52% of the patients with anticoagulants and catheter ablation was performed in 8.9% of the enrolled patients. The change in the prescription rate of DOACs and the performing rate of catheter ablation in these registry studies reflected the recent changes in the treatment of AF in Japan. Several studies that have presented the superiority of catheter ablation and DOACs compared to medical therapy and warfarin will further accelerate this therapeutic transition. The patient background of the HAF‐NET Registry is characterized by a very high catheter ablation‐performing rate along with the recent high‐prescription rate of NOACs. Ischemic strokes/systemic embolisms and major bleeding occurred in 0.6% and 0.8% of patients in the HAF‐NET Registry during 1‐year of follow‐up, which was an extremely low incidence. Although it was not significant, the history of AF tended to reduce the composite endpoint of ischemic strokes/systemic embolisms and fatal bleeding. In the Fushimi AF registry, strokes/systemic embolisms and major bleeding occurred in 2.6%/year and 1.5%/year of patients with oral anticoagulants, and 2.1%/year and 1.4%/year of patients without oral anticoagulants.2 The SAKURA AF Registry also showed no significant difference in the rate of the strokes/systemic embolisms and the major bleeding rate between the DOACs and warfarin users (1.2% vs 1.8%/year and 0.5% vs 1.2%/year, respectively).3 Furthermore, fewer anticoagulant drugs were used in the patients with a catheter ablation history (anticoagulant use: 71.5% vs 93.6%, P < .001) in the HAF‐NET Registry. The CABANA study had a lower rate of disabling strokes in the catheter ablation group compared to the drug therapy group, but there was no significant difference (0.3% vs 0.6%, P = .1). The rate of major bleeding was almost the same between the two groups (3.2% vs 3.3%, P = .7).4 The high‐performing rate of catheter ablation and discontinuation of anticoagulation therapy after catheter ablation might lead to a lower stroke/systemic embolism and major bleeding rate in the HAF‐NET Registry. Although the evidence is not clear, the benefit of catheter ablation may also be the discontinuation of anticoagulant therapy after ablation in low‐risk patients for ischemic strokes. In the HAF‐NET Registry, secondary endpoints included a composite of new‐onset dementia, cardiac events requiring hospitalization, and all‐cause death. Because the independent predictors of new‐onset dementia were the age and diabetes mellitus, which have already been well‐known, the significance of adding new‐onset dementia to the secondary endpoints as well as cardiac events requiring