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

Chan, Yi-Hsin, Chao, Tze-Fan, Chen, Shao-Wei, Lee, Hsin-Fu, Yeh, Yung-Hsin, Huang, Ya-Chi, Chang, Shang-Hung, Kuo, Chi-Tai, Lip, Gregory YH ORCID: 0000-0002-7566-1626 and Chen, Shih-Ann (2020) Off-label dosing of non-vitamin K antagonist oral anticoagulants and clinical outcomes in Asian patients with atrial fibrillation. HEART RHYTHM, 17 (12). pp. 2102-2110.

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Abstract

<h4>Background</h4>Off-label dosing non-vitamin K antagonist oral anticoagulants (NOACs) are commonly prescribed for Asian patients with atrial fibrillation (AF).<h4>Objective</h4>The purpose of this study was to investigate the associations between inappropriate dosing of NOACs and clinical outcomes.<h4>Methods</h4>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.<h4>Results</h4>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 <.001), whereas overdosing NOACs were associated with a significantly higher risk of major bleeding (aHR 2.01; 95% CI 1.13-3.56; P = .017). Compared to warfarin, the 4 on-label dosing NOACs were associated with a comparable risk of IS/SE and a significantly lower risk of major bleeding, whereas underdosing NOACs were associated with a higher risk of IS/SE (aHR 1.46; P = .012).<h4>Conclusion</h4>About 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, whereas overdosing was associated with a higher risk of major bleeding. Thus, even for Asian AF patients at higher risk for bleeding, NOACs still should be prescribed at the dosing based on clinical trial criteria and guideline recommendations.

Item Type:	Article
Uncontrolled Keywords:	Asian, Atrial fibrillation, Dosing, Non-vitamin K antag-onist oral anticoagulant, Outcomes
Depositing User:	Symplectic Admin
Date Deposited:	29 Sep 2020 07:14
Last Modified:	18 Jan 2023 23:31
DOI:	10.1016/j.hrthm.2020.07.022
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3102949