The Reversal of Bleeding Caused by New Oral Anticoagulants (NOACs): A Systematic Review and Meta-Analysis

Abstract

New oral anticoagulants (NOACs; ie, direct thrombin inhibitor [DTI] and factor Xa [FXa] inhibitors) were used as alternatives to warfarin. Specific antidotes (idarucizumab for dabigatran and andexanet alfa for FXa inhibitors) and hemostatic reversal agents were used for lowering bleeding, but their efficacies were still uncertain. The objectives of this study were to estimate and compare the efficacy of NOAC antidotes on bleeding reversal and death. Studies were identified from MEDLINE and Scopus databases until May 2018. Case reports/series and cohorts were selected if they assessed reversal or death rates. Data were independently extracted by 2 reviewers. Individual patient data and aggregated data of outcomes were extracted from case reports/series and cohorts. Binary regression was used to estimate outcome rates, risk ratio (RR) along with 95% confidence interval (CI). Interventions were NOACs and reversal agents (ie, DTI-specific, DTI-standard, FXa-specific, and FXa-standard). Among 220 patients of 93 case reports/series, reversal rates were 95.9%, 77.6%, and 71.5% for DTI-specific, FXa-standard, and DTI-standard. Pooled RRs for DTI-specific and FXa-standard versus DTI-standard, respectively, were 1.34 (CI: 1.13-1.60) and 1.09 (CI: 0.84-1.40). Death rate was 0.18 (CI: 0.06-0.57) times lower in DTI-specific versus DTI-standard. For pooling 10 subcohorts, pooled RRs were 1.08 (CI: 1.00-1.16), 1.29 (CI: 1.20-1.39), and 1.13 (CI: 1.01-1.25) for DTI-specific, FXa-specific, and FXa-standard versus DTI-standard. In conclusion, specific reversal agents might be useful for reversal of bleeding and lowering the risk of death than standard reversal agents. Our findings were based on case reports/series and selected cohorts, further comparative studies are thus needed.