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      Efficacy and Safety of Apixaban, Dabigatran, Rivaroxaban, and Warfarin in Asians With Nonvalvular Atrial Fibrillation

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          Abstract

          Background

          Whether non–vitamin K antagonist oral anticoagulants ( NOACs) are superior to warfarin among Asians with nonvalvular atrial fibrillation remains unclear.

          Methods and Results

          In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, there were 5843, 20 079, 27 777, and 19 375 nonvalvular atrial fibrillation patients taking apixaban, dabigatran, rivaroxaban and warfarin, respectively, from June 1, 2012 to December 31, 2016. Propensity‐score weighting was used to balance covariates across study groups. Patients were followed until the first occurrence of any efficacy or safety outcome or the end date of study. Hazard ratios (95% confidence intervals) comparing apixaban, dabigatran, and rivaroxaban with warfarin were: ischemic stroke/systemic embolism ( IS/ SE), 0.55 (0.43–0.69), 0.82 (0.68–0.98), and 0.81 (0.67–0.97); major bleeding, 0.41 (0.31–0.53), 0.65 (0.53–0.80), and 0.58 (0.46–0.72); and all‐cause mortality, 0.58 (0.51–0.66), 0.61 (0.54–0.68), and 0.57 (0.51–0.65). A total of 3623 (62%), 17 760 (88%), and 26 000 (94%) patients were taking low‐dose apixaban (2.5 mg twice daily), dabigatran (110 mg twice daily), and rivaroxaban (10–15 mg once daily), respectively. Similar to all‐dose NOACs, all low‐dose NOACs had lower risk of IS/ SE, major bleeding, and mortality when compared with warfarin. In contrast to other standard‐dose NOACs, apixaban was associated with lower risks of IS/ SE (0.45 [0.31–0.65]), major bleeding (0.29 [0.18–0.46]), and mortality (0.23 [0.17–0.31]) than warfarin.

          Conclusions

          All NOACs were associated with lower risk of IS/ SE, major bleeding, and mortality compared with warfarin in the largest real‐world practice among Asians with nonvalvular atrial fibrillation. All low‐dose NOACs had lower risk of IS/ SE, major bleeding, and mortality when compared with warfarin. Standard‐dose apixaban caused a lower risk of IS/ SE, major bleeding, and mortality compared with warfarin.

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          Most cited references22

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          Non-Vitamin K Antagonist Oral Anticoagulant Dosing in Patients With Atrial Fibrillation and Renal Dysfunction.

          Dose reduction of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in patients with atrial fibrillation (AF) with renal impairment. Failure to reduce the dose in patients with severe kidney disease may increase bleeding risk, whereas dose reductions without a firm indication may decrease the effectiveness of stroke prevention.
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            Off-Label Dosing of Non-Vitamin K Antagonist Oral Anticoagulants and Adverse Outcomes: The ORBIT-AF II Registry.

            Although non-vitamin K antagonist oral anticoagulants (NOACs) do not require frequent laboratory monitoring, each compound requires dose adjustments on the basis of certain clinical criteria.
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              Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –.

              The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15 mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; P<0.001 [non-inferiority]). Intracranial hemorrhage rates were 0.8% with rivaroxaban and 1.6% with warfarin. There was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban vs. warfarin (HR, 0.49; P=0.050). J-ROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice.
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                Author and article information

                Contributors
                chitai@cgmh.org.tw
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                05 April 2018
                17 April 2018
                : 7
                : 8 ( doiID: 10.1002/jah3.2018.7.issue-8 )
                : e008150
                Affiliations
                [ 1 ] Cardiovascular Department Chang Gung Memorial Hospital Linkou, Taoyuan Taiwan
                [ 2 ] Division of Rheumatology, Allergy and Immunology Department of Internal Medicine Chang Gung Memorial Hospital Linkou, Taoyuan Taiwan
                [ 3 ] College of Medicine Chang Gung University Taoyuan Taiwan
                [ 4 ] Department of Public Health College of Medicine Chang Gung University Taoyuan Taiwan
                [ 5 ] Biostatistics Core Laboratory Molecular Medicine Research Center Chang Gung University Taoyuan Taiwan
                Author notes
                [*] [* ] Correspondence to: Chi‐Tai Kuo, MD, FAHA, The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. E‐mail: chitai@ 123456cgmh.org.tw
                Article
                JAH33089
                10.1161/JAHA.117.008150
                6015442
                29622587
                026786b4-d815-4d2e-9369-def4edb96b1a
                © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 January 2018
                : 01 March 2018
                Page count
                Figures: 7, Tables: 5, Pages: 16, Words: 9791
                Funding
                Funded by: Ministry of Science and Technology
                Award ID: 102‐2628‐B‐182‐011‐MY3
                Award ID: 102‐2314‐B‐182A‐053‐MY3
                Award ID: 105‐2628‐B‐182A‐003‐MY3
                Funded by: Chang Gung Memorial Hospital, Linkou, Taiwan
                Award ID: CMRPG3B0991‐3
                Award ID: CMRPG3E1681
                Award ID: CMRPG3F0041
                Award ID: CMRPG3F0853
                Award ID: CMRPG3D1631
                Award ID: CMRPD1F0252
                Award ID: CMRPG3F0041
                Award ID: CMRPG3E0291
                Categories
                Original Research
                Original Research
                Arrhythmia and Electrophysiology
                Custom metadata
                2.0
                jah33089
                17 April 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.4 mode:remove_FC converted:17.04.2018

                Cardiovascular Medicine
                atrial fibrillation,direct thrombin inhibitor,factor xa inhibitor,hemorrhage,ischemic stroke,mortality,warfarin,intracranial hemorrhage

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