Current Real-World Status of Off-Label Under- and Over-Dose of Direct Oral Anticoagulants After Atrial Fibrillation Ablation

Off-label under- and overdosing of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) is not uncommon in real-world practice. This study aimed to identify efficacy and safety of off-label DOACs dose after AF ablation. The RYOUMA registry was a prospective multicenter study of Japanese patients who underwent AF ablation between 2017 and 2018. DOAC prescriptions were categorized into on-label standard dose, on-label reduced dose, off-label underdose, and off-label overdose. The proportion of off-label doses among patients after AF ablation varied depending on the type of DOAC, ranging from 13.5% to 34.9%. Of 2821 patients, 366 (13.0%) were prescribed an off-label underdose and exhibited significantly higher CHADS , CHA DS -VASc, CHA DS -VA, HELT-E S , and HAS-BLED scores, age, concomitant use of antiplatelets, and lower weight when compared to the on-label standard dose (n = 1809). While the incidence of ischemic stroke after 1 year of off-label underdose was notably low (0.28%), the rate of major bleeding was relatively high (1.7%). Off-label overdose was prescribed to 134 patients (4.8%), who showed a significantly higher incidence of major bleeding (3.0%) compared to on-label standard dose (0.91%; p = 0.02). The off-label overdose group did not have any particular background and its thromboembolic risk was, conversely, low. The most likely cause of off-label overdose was clinicians potentially overlooking dose criteria, including advanced age, low body weight, and low creatinine clearance. In patients after AF ablation, off-label DOAC overdose was infrequent, but significantly associated with higher incidence of major bleeding during the remote period after AF ablation. The study was registered as UMIN000026092 (University Hospital Medical Information Network-Clinical Trial Registry).