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

Background: Off-label under- and overdosing of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) is not uncommon in real-world practice.

Objective: This study aimed to identify efficacy and safety of off-label DOACs dose after AF ablation.

Methods: 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.

Results: 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 CHADS₂, CHA₂DS₂-VASc, CHA₂DS₂-VA, HELT-E₂S₂, 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.

Conclusions: 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.

Trial registration: The study was registered as UMIN000026092 (University Hospital Medical Information Network-Clinical Trial Registry).