Chun-Li Wang1,2, Victor Chien-Chia Wu1,2, Kuo-Hsuan Chang2,3, Hui-Tzu Tu4, Chang-Fu Kuo2,5,6, Yu-Tung Huang4,7, Pao-Hsien Chu1,2, Chi-Ching Kuo8, Shang-Hung Chang1,2,4,7. 1. Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, No. 5, Fushin St. Kweishan District, 33305 Taoyuan City, Taiwan. 2. College of Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Kweishan District, 33302 Taoyuan City, Taiwan. 3. Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, No. 5, Fushin St. Kweishan District, 33305 Taoyuan City, Taiwan. 4. Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Linkou Medical Center, No. 5, Fushin St. Kweishan District, 33305 Taoyuan City, Taiwan. 5. Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, No. 5, Fushin St. Kweishan District, 33305 Taoyuan City, Taiwan. 6. Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK. 7. Graduate Institute of Nursing, Chang Gung University of Science and Technology, No. 261, Wenhua 1st Road, Kweishan District, 33302 Taoyuan City, Taiwan. 8. Institute of Organic and Polymeric Materials, National Taipei University of Technology, No. 1, Section 3, Zhongxiao E Rd, Da-an District, 10607 Taipei, Taiwan.
Abstract
AIMS: This study compared the risk of major bleeding between atrial fibrillation (AF) patients who took non-vitamin K antagonist oral anticoagulants (NOACs) and antiepileptic drugs (AEDs) concurrently and those who took only NOACs. METHODS AND RESULTS: We performed a retrospective cohort study using Taiwan National Health Insurance database and included AF patients who received NOAC prescriptions from 1 June 2012 to 31 December 2017. The major bleeding risks of person-quarters exposed to NOAC and 11 concurrent AEDs (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, topiramate, valproic acid, and zonisamide) were compared with person-quarters exposed to NOAC alone. Adjusted incidence rate differences between NOAC with or without concurrent AEDs were estimated using Poisson regression models weighted by the inverse probability of treatment. Among 104 319 patients (age 75.0 ± 10.3 years; men, 56.2%), 8546 major bleeding events occurred during 731 723 person-quarters with NOAC prescriptions. Concurrent AED use was found in 15.3% of NOAC-treated patients. Concurrent use of NOAC with valproic acid, phenytoin, or levetiracetam increased adjusted incidence rates per 1000 person-years of major bleeding more significantly than NOAC alone: 153.49 for NOAC plus valproic acid vs. 55.06 for NOAC alone [difference 98.43, 95% confidence interval (CI) 82.37-114.49]; 135.83 for NOAC plus phenytoin vs. 54.43 for NOAC alone (difference 81.4, 95% CI 60.14-102.66); and 132.96 for NOAC plus levetiracetam vs. 53.08 for NOAC alone (difference 79.88, 95% CI 64.47-95.30). CONCLUSION: For AF patients, the concurrent use of NOACs and valproic acid, phenytoin, or levetiracetam was associated with a higher risk of major bleeding. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: This study compared the risk of major bleeding between atrial fibrillation (AF) patients who took non-vitamin K antagonist oral anticoagulants (NOACs) and antiepileptic drugs (AEDs) concurrently and those who took only NOACs. METHODS AND RESULTS: We performed a retrospective cohort study using Taiwan National Health Insurance database and included AFpatients who received NOAC prescriptions from 1 June 2012 to 31 December 2017. The major bleeding risks of person-quarters exposed to NOAC and 11 concurrent AEDs (carbamazepine, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, pregabalin, topiramate, valproic acid, and zonisamide) were compared with person-quarters exposed to NOAC alone. Adjusted incidence rate differences between NOAC with or without concurrent AEDs were estimated using Poisson regression models weighted by the inverse probability of treatment. Among 104 319 patients (age 75.0 ± 10.3 years; men, 56.2%), 8546 major bleeding events occurred during 731 723 person-quarters with NOAC prescriptions. Concurrent AED use was found in 15.3% of NOAC-treated patients. Concurrent use of NOAC with valproic acid, phenytoin, or levetiracetam increased adjusted incidence rates per 1000 person-years of major bleeding more significantly than NOAC alone: 153.49 for NOAC plus valproic acid vs. 55.06 for NOAC alone [difference 98.43, 95% confidence interval (CI) 82.37-114.49]; 135.83 for NOAC plus phenytoin vs. 54.43 for NOAC alone (difference 81.4, 95% CI 60.14-102.66); and 132.96 for NOAC plus levetiracetam vs. 53.08 for NOAC alone (difference 79.88, 95% CI 64.47-95.30). CONCLUSION: For AFpatients, the concurrent use of NOACs and valproic acid, phenytoin, or levetiracetam was associated with a higher risk of major bleeding. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Matteo Candeloro; John W Eikelboom; Noel Chan; Vinai Bhagirath; James D Douketis; Sam Schulman Journal: Res Pract Thromb Haemost Date: 2022-02-17
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