Off-label dosing of non–vitamin K antagonist oral anticoagulants and clinical outcomes in Asian patients with atrial fibrillation

Off-label dosing non–vitamin K antagonist oral anticoagulants (NOACs) are commonly prescribed for Asian patients with atrial fibrillation (AF). The purpose of this study was to investigate the associations between inappropriate dosing of NOACs and clinical outcomes. We used medical data from a multicenter health care system in Taiwan, which included 2068, 5135, 2589, 1483, and 2342 AF patients taking dabigatran, rivaroxaban, apixaban, edoxaban, and warfarin, respectively. The risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding in patients treated with underdosing or overdosing NOACs were compared to those of on-label dosing NOACs and warfarin. About 27% and 5% of AF patients were treated with underdosing and overdosing NOACs, respectively. Compared to on-label dosing, underdosing NOACs were associated with a significantly higher risk of IS/SE (adjusted hazard ratio [aHR] 1.59; 95% confidence interval [CI] 1.25–2.02; P