Standard dose versus low dose non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: A meta-analysis of contemporary randomized controlled trials.
Although randomized controlled trials (RCTs) indicated that standard dose non-vitamin K antagonist oral anticoagulants (NOACs) were more compelling, low dose NOACs are commonly used in clinical practice in Asia.



The purpose of this study was to assess the relative therapeutic benefit and risk of standard dose vs low dose NOACs in Asian patients enrolled in contemporary RCTs.



We performed a prespecified meta-analysis of 3155 Asian patients with NOACs in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) and ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trials. Efficacy and safety with standard dose vs low dose NOACs were compared by risk ratios (RRs) and 95% confidence intervals (CIs) in a random-effects model. An evidence network incorporating additional Asian patients from ROCKET AF, J- ROCKET AF, and ARISTOTLE was constructed with the Bayesian method.



Risks of stroke or systemic embolism and ischemic stroke were significantly reduced with standard dose vs low dose NOACs (RR 0.62, 95% CI 0.45-0.85; and RR 0.55, 95% CI 0.38-0.79, respectively). Rates of major, intracranial, and life-threatening bleeding with 2 dosing regimens were broadly similar (RR 1.31, 95% CI 0.74-2.33; RR 1.54, 95% CI 0.72-3.30; and RR 1.49, 95% CI 0.87-2.55, respectively). Absolute rates of all-cause mortality and the net clinical outcome with standard dose NOACs were lower but not statistically significant (absolute reduction 0.4% per year and 1.1% per year, respectively). Network meta-analyses demonstrated that standard dose NOACs had the most favorable risk-benefit profile among oral anticoagulants.



In Asian patients, standard dose NOACs represent a more appealing therapeutic option than low dose NOACs, with a significant reduction in ischemic stroke without an excess of major bleeding.
General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Kang-Ling
KL
Wang
Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Robert P
RP
Giugliano
Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan.
Shinya
S
Goto
School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Chun-Chih
CC
Chiu
School of Nursing, National Yang-Ming University, Taipei, Taiwan.
Chun-Yi
CY
Lin
Institute of Information Science, Academia Sinica, Taipei, Taiwan.
En-Yu
EY
Lai
General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: cechiang@vghtpe.gov.tw.
Chern-En
CE
Chiang
D000925:Anticoagulants / Q000494:pharmacology*; D044466:Asian People; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy / Q000208:ethnology; D004305:Dose-Response Relationship, Drug; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000209:etiology / Q000517:prevention & control
D000925:Anticoagulants
Anticoagulant; Asian patients; Atrial fibrillation; Hemorrhage; Stroke