Prescriptions of off-label dosing non-vitamin K antagonist oral anticoagulants (NOACs) are common for Asian patients with atrial fibrillation (AF).
To investigate the associations between inappropriate dosing of NOACs and clinical outcomes.
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.
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<.001), while over-dosing NOACs were associated with a significantly higher risk of major bleeding (aHR 2.01, 95%CI 1.13-3.56; P=0.017). Compared to warfarin, the four on-label dosing NOACs were all associated with a comparable risk of IS/SE and a significantly lower risk of major bleeding, while under-dosing NOACs were associated with a higher risk of IS/SE (aHR 1.46; P=0.012).
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.
Copyright © 2020. Published by Elsevier Inc.