Once- or twice-daily non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: A meta-analysis of randomized controlled trials.

BACKGROUND/PURPOSE: Non-vitamin K antagonist oral anticoagulants (NOACs) have a half-life of around 12 h. We aimed to clarify if there was any effect modification by dosing (once- or twice-daily) regimens in Asian patients. METHODS: Phase III randomized controlled trials of NOACs compared with warfarin in Asian patients with atrial fibrillation (AF) were identified and extracted from PubMed, CENTRAL, and CINAHL databases through November 2016. Outcomes were pooled by dosing regimens with the Mantel-Haenszel fixed-effects model. The risk ratio (RR) and 95% confidence interval (CI) were calculated. Effect differences between once- and twice-daily NOACs were assessed with Bucher indirect comparisons using common estimates, once heterogeneity was low, and with the Bayesian method. RESULTS: From 6 trials, there was no effect modification by dosing regimens in the risk of stroke or systemic embolism across ethnicities (all interaction P > 0.05). Both dosing regimens were associated with a greater reduction in the risk of major bleeding in Asian patients (RR, 0.63 (95% CI, 0.47-0.85) and 0.57 (95% CI, 0.43-0.75), for once- and twice-daily NOACs, respectively). In Asian patients, risks of hemorrhagic stroke and intracranial hemorrhage were lower with once- (RR, 0.41 (95% CI, 0.21-0.80) and 0.29 (95% CI, 0.16-0.53)) and twice-daily NOACs (RR, 0.25 (95% CI, 0.12-0.51) and 0.38 (95% CI, 0.23-0.65)), compared with warfarin. There was no effect difference favoring any of NOAC regimens evaluated by Bucher and Bayesian methods. CONCLUSION: In Asian patients with AF, NOACs, regardless of dosing regimens, have a similar feature of preserved efficacy with improved safety compared with warfarin.