Off-Label Dosing of Non-Vitamin K Antagonist Oral Anticoagulants and Clinical Outcomes in Asian Patients with Atrial Fibrillation

Abstract Background Prescriptions of off-label dosing non-vitamin K antagonist oral anticoagulants (NOACs) are common for Asian patients with atrial fibrillation (AF). Objective To investigate the associations between inappropriate dosing of NOACs and clinical outcomes. Methods We used medical data from a multi-center healthcare system in Taiwan including 2,068, 5,135, 2,589, 1,483, and 2,342 AF patients taking dabigatran, rivaroxaban, apixaban, edoxaban and warfarin, respectively. The risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding of patients treated with under-dosing or over-dosing NOACs were compared to on-label dosing NOACs and warfarin. Results Around 27% and 5% of AF patients were treated with under-dosing and over-dosing NOACs, respectively. Compared to on-label dosing, under-dosing NOACs were associated with a significantly higher risk of IS/SE (aHR 1.59, 95%CI 1.25-2.02; P Conclusions Around 3 in 10 Asian AF patients were treated with off-label dosing NOACs in daily practice. Compared to on-label dosing, underdosing was associated with a higher risk of IS/SE, while overdosing was associated with a higher risk of major bleeding. Even for Asian AF patients at a higher risk of bleeding, NOACs should still be prescribed at the dosing following clinical trial criteria and guideline recommendations.