Yi-Hsin Chan1, Tze-Fan Chao2, Shao-Wei Chen3, Hsin-Fu Lee4, Yung-Hsin Yeh5, Ya-Chi Huang6, Shang-Hung Chang7, Chi-Tai Kuo1, Gregory Y H Lip8, Shih-Ann Chen9. 1. Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Microscopy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. 2. Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan. Electronic address: eyckeyck@gmail.com. 3. Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan City, Taiwan; Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan. 4. Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 5. Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan. 6. Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan. 7. Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City, Taiwan. 8. Liverpool Centre for Cardiovascular Science, University of Liverpool & Liverpool Heart and Chest Hospital, Liverpool, United Kingdom; Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. 9. Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
Abstract
BACKGROUND: Off-label dosing non-vitamin K antagonist oral anticoagulants (NOACs) are commonly prescribed for Asian patients with atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to investigate the associations between inappropriate dosing of NOACs and clinical outcomes. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
BACKGROUND: Off-label dosing non-vitamin K antagonist oral anticoagulants (NOACs) are commonly prescribed for Asian patients with atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to investigate the associations between inappropriate dosing of NOACs and clinical outcomes. METHODS: We used medical data from a multicenter health care system in Taiwan, which included 2068, 5135, 2589, 1483, and 2342 AFpatients 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. RESULTS: About 27% and 5% of AFpatients 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). CONCLUSION: About 3 in 10 Asian AFpatients 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 AFpatients at higher risk for bleeding, NOACs still should be prescribed at the dosing based on clinical trial criteria and guideline recommendations.
Authors: Antonio González-Pérez; Luke Roberts; Pareen Vora; Maria Eugenia Saez; Gunnar Brobert; Samuel Fatoba; Luis Alberto García Rodríguez Journal: BMJ Open Date: 2022-06-02 Impact factor: 3.006