Comparison of Efficacy and Safety of Direct Oral Anticoagulants and Warfarin between Patients in Asian and non-Asian Regions: A Systematic Review and Meta-Regression Analysis.

Direct oral anticoagulants (DOACs) have increasingly replaced warfarin for treating patients with non-valvular atrial fibrillation (NVAF). DOACs have been demonstrated to be more useful than warfarin which was highlighted at its ethnic differences in efficacy and safety; however, the regional differences of DOACs remain unclear. We conducted a systematic review, meta-analysis, and meta-regression to evaluate the efficacy and safety of DOACs in patients from Asian and non-Asian regions with NVAF. We systematically searched randomized control trials published before August 2019. We defined 11 studies comprising 7,118 Asian and 53,282 non-Asian patients, totaling 60,400 NVAF patients. The risk ratios (RRs) of DOACs were calculated against warfarin. The efficacy of DOACs was significantly higher in Asian regions regarding stroke/systemic embolism events (RR: 0.62 and 95% confidence interval (CI): 0.49-0.78 for Asian regions; RR: 0.83 and 95% CI: 0.75-0.92 for non-Asian regions; P interaction: 0.02), when compared with warfarin. The safety of DOACs was significantly higher in Asian regions regarding major bleeding (RR: 0.62 and 95% CI: 0.51-0.75 for Asian regions; RR: 0.90 and 95% CI: 0.76-1.05 for non-Asian regions; P interaction: 0.004), compared with warfarin. In addition, we conducted meta-regression analysis to discuss the true regional differences of DOACs to warfarin. The meta-regression analysis, which adjusts the effect of individual backgrounds in each study, indicated that the regional differences were observed in the efficacy but not in drug safety. These results suggest that treatment with DOACs may be more effective than the conventional warfarin in the Asian region.