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.

American College of Gastroenterology-Canadian Association of Gastroenterology Clinical Practice Guideline: Management of Anticoagulants and Antiplatelets During Acute Gastrointestinal Bleeding and the Periendoscopic Period

“…However, the mortality results were not adjusted for confounding, and the comparator group's death rate is unknown. Several systematic reviews (33)(34)(35) have reported mainly on low-quality, single-arm cohort studies.…”

A review of guidelines on anticoagulation reversal across different clinical scenarios – Is there a general consensus?

“…However, one meta-analysis (including 10 case series) reported that it was difficult to assess whether the addition of 4F-PCCs was more effective in managing major bleeding compared with cessation of DOAC therapy alone [ 63 ]. Another meta-analysis compared anticoagulant reversal rates for non-specific and specific reversal agents, reporting that patients on Factor Xa inhibitors generally experienced higher reversal rates compared with patients on dabigatran; reversal rates were highest in each case when a specific reversal agent was used [ 64 ]. Activated PCC was also shown to be effective in reversing DOAC anticoagulation due to bleeding or requirement for urgent surgical intervention, with TEE rates ranging from 8 to 10% [ 65 , 66 ].…”

Beyond Anticoagulation: A Comprehensive Review of Non-Vitamin K Oral Anticoagulants (NOACs) in Inflammation and Protease-Activated Receptor Signaling

“…In comparison to warfarin, which has a wide range of drug interactions, NOACs have a notably reduced profile of interactions with other medications [18]. Additionally, certain NOACs come with the option of specific antidotes for rapid reversal in the event of bleeding complications, offering an extra layer of safety in emergency situations [19]. NOACs targeting Factor Xa include the drugs: rivaroxaban, apixaban, edoxaban, and betrixaban.…”