Safety of direct oral anticoagulants in patients with cirrhosis: a systematic review and meta-analysis.

Introduction Direct oral anticoagulants (DOACs) are effective treatment for venous thromboembolism. However, safety data in patients with cirrhosis are limited. We conducted a systematic review and meta-analysis to evaluate the safety of DOACs compared with warfarin or low-molecular weight heparin in patients with cirrhosis. Methods A systematic literature search was performed using MEDLINE and EMBASE from inception up to June 2018. We included prospective and retrospective studies involving adults ≥18 years with cirrhosis in whom anticoagulants were indicated for any indications. Primary outcome was all-cause bleeding events. Secondary outcome was major bleeding. Pooled risk ratio, pooled odd ratios and 95% confidence intervals (CIs) were calculated using random-effects model. Results Five studies with a total of 447 patients were included in the analysis. When compared with controls, the use of DOACs in cirrhotic patients did not show a significant difference in all-cause bleeding (risk ratio 0.72; 95% CI, 0.32-1.63). There was also no significant difference in major bleeding between both groups (odd ratio 0.46; 95% CI, 0.10-2.09). Conclusions Our study demonstrates that, compared to those who were treated with traditional anticoagulants, cirrhotic patients who were treated with DOACs had no significant increase risk of all-cause bleeding and major bleeding.