The first direct oral anticoagulant (DOAC) was approved nearly a decade ago, yet there remains apprehension in transitioning to wide-spread use despite demonstrated efficacy and ease of use. One limitation is the absence of a reversal agent for patients on DOACs who develop significant bleeding or require emergent surgery. Idarucizumab is a humanized monoclonal antibody fragment which binds dabigatran and rapidly reverses anticoagulant activity.
The Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD) multicenter prospective single-cohort study enrolled 503 patients taking dabigatran with uncontrollable or life threatening bleeding (Group A, n = 301) or need for urgent surgical or invasive procedures (Group B, n = 202) to receive a standard dose of idarucizumab 5 g intravenously. A control group was not included based on pretrial investigations demonstrating safety and efficacy in reversing dabigatran, and withholding the drug was regarded as unethical.
The primary endpoint was maximum percentage reversal of anticoagulant effect based on diluted thrombin time (dTT) or ecarin clotting time (ECT) with complete reversal defined as a decrease in dTT or ECT to normal level. Of the 461 patients with abnormal baseline dTT or ECT, 100% experienced complete reversal within 4 hours of administration. This effect was sustained for 24 hours in the majority of patients, with only 9 (1.8%) patients requiring additional doses of Idarucizumab. Secondary endpoints were restoration of hemostasis and safety measures, which were generally favorable.
Safety concerns included thrombotic events necessitating re-initiation of anticoagulation (4.8% at 30 days, 6.8% at 90 days) and hypersensitivity to the medication (0.6%).
Administration of idarucizumab in patients on dabigatran resulted in rapid anticoagulant reversal with a very tolerable risk of thromboembolic complications given the high acuity scenarios for which reversal was provided. Whether or not the availability of Idarucizumab effects utilization rates of Dabigatran relative to Coumadin or other DOACs remains to be seen.
Pollack CV Jr, Reilly PA, va Ryn J, et al. “Idarucizumab for Dabigatran Reversal- Full Cohort Analysis.” N Engl J Med. 2017 Aug 3;377(5):431-441
Tara Jones, MD PharmD and James M. McCabe, MD
University of Washington, Seattle, USA