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.

BACKGROUND: 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.

OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.