Dabigatran Reversal With Idarucizumab in Patients Requiring Urgent Surgery

A Subanalysis of the RE-VERSE AD Study

Jerrold H. Levy, MD; Joanne van Ryn, PhD; Frank W. Sellke, MD; Paul A. Reilly, PhD; Amelie Elsaesser, PhD; Stephan Glund, PhD; Jörg Kreuzer, MD; Jeffrey I. Weitz, MD; Charles V. Pollack Jr., MD, MA

Disclosures

Annals of Surgery. 2021;274(3):e204-e211. 

In This Article

Abstract and Introduction

Abstract

Objective: To further examine anticoagulation reversal and clinical outcomes in dabigatran treated patients requiring urgent surgery or procedural interventions.

Background: Idarucizumab, a humanized monoclonal antibody fragment, reverses dabigatran anticoagulation.

Methods: Data from surgical and procedural patients in RE-VERSE AD, a multicenter, open-label, single-arm, prospective cohort of dabigatran reversal were evaluated. A total of 202 patients in this group received 5 g of idarucizumab before surgery or procedures.

Results: The interventions included 49 abdominal, 45 orthopedic, 34 vascular, 8 neurologic, and 4 genitourinary surgical procedures, or 29 catheter-based cases, 20 cases for drainage, and 8 diagnostic procedures. Five patients did not undergo their intended intervention after receiving idarucizumab. Complete reversal of the dabigatran anticoagulant effect occurred within minutes in almost all patients, with normal hemostasis in more than 91% of patients. The median time from the first vial of idarucizumab to surgery or procedures was less than 2 hours in all groups except neurosurgery, where it was 3.3 hours. Fresh frozen plasma and packed red cells were the most frequently transfused blood products. Postreversal thromboembolic events occurred in 10 (5%) patients at 30 days, 5 of whom had restarted anticoagulation before the event. Overall 30-day mortality was 12.6%. There were no serious adverse safety signals due to idarucizumab dosing.

Conclusions: Idarucizumab facilitates management of patients requiring urgent procedures by providing rapid dabigatran reversal, and is the only agent of its class studied in surgical patients.

Introduction

Patients undergoing urgent or emergent surgery are at high risk of bleeding due to multiple factors including tissue injury, dilutional coagulopathy, and coagulation factor consumption.[1,2] If patients are taking oral anticoagulants, the risk increases further and many interventions are delayed or if they cannot wait, are performed but with the potential for increased bleeding risks. Consequently, anticoagulant reversal before urgent interventions may improve management by reducing the risk of bleeding.[3] Currently available oral anticoagulants include vitamin K antagonists, such as warfarin, and direct oral anticoagulants (DOACs), such as dabigatran, apixaban, and rivaroxaban. Specific strategies for reversing anticoagulation include vitamin K and 4-factor prothrombin complex concentrate for warfarin, dabigatran with idarucizumab, and factor Xa inhibitors with andexanet alfa.[4] Of the DOAC reversal agents, idarucizumab is the only agent studied and licensed for dabigatran reversal in patients requiring urgent surgery or intervention as andexanet alfa has yet to be evaluated in this setting.

Idarucizumab is a humanized Fab fragment that binds dabigatran with high affinity[5] that was evaluated in the Reversal Effects of Idarucizumab in Patients on Active Dabigatran (RE-VERSE AD) study, which enrolled 503 dabigatran-treated patients presenting with life-threatening bleeding (group A) or requiring urgent surgery or intervention (group B). As previously reported, idarucizumab produced a rapid, complete, and sustained reversal of the anticoagulant effects of dabigatran.[6] In this analysis, we further examined the 202 patients in group B who received idarucizumab before urgent surgery or procedural interventions.

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