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Idarucizumab for Dabigatran Reversal
Study Questions:
Does idarucizumab, an antibody fragment, reverse the anticoagulant effects of dabigatran?
Methods:
Using a prospective cohort design, the RE-VERSE AD (Reversal Effects of Idarucizumab on Active Dabigatran) study authors examined the safety of idarucizumab 5 mg administered intravenously in two 2.5 g boluses no more than 15 minutes apart. Patients were included if they were experiencing serious bleeding (group A) or required an urgent procedure (group B). The primary endpoint was the maximal percent reversal of dabigatran’s anticoagulant effect within 4 hours after administering idarucizumab, as determined by the dilute thrombin time or ecarin clotting time. The secondary endpoint included restoration of hemostasis. This report is an interim analysis of the first 90 patients treated with idarucizumab from this cohort study.
Results:
Of the 90 patients receiving idaricizumab, 51 were treated for serious bleeding, while 39 were treated for an urgent procedure. Of the 90 study patients, 29 (32%) were treated with dabigatran 150 mg twice daily, while 58 (64%) were treated with dabigatran 110 mg twice daily. Sites of serious bleeding (group A) included gastrointestinal for 20 patients (39%), intracranial for 18 patients (35%), and trauma related for nine patients (18%). Of the 68 (76%) patients with an elevated dilute thrombin time and the 81 (90%) patients with an elevated ecarin clotting time at baseline, median maximal percent reversal was 100% (95% confidence interval, 100-100%). Normalization of thrombotic tests was achieved in 88-98% of patients, and occurred within minutes of drug administration. The concentration of unbound dabigatran remained below 20 ng/ml at 24 hours in 79% of patients. Hemostasis was achieved in 33/35 of the group A (serious bleeding) patients in whom it could be assessed. One thrombotic event occurred within 72 hours after idarucizumab was administered in a patient for whom anticoagulants had not been reinitiated.
Conclusions:
The authors concluded that idarucizumab completely and rapidly reversed the anticoagulant effect of dabigatran among patients with serious bleeding or requiring urgent procedures.
Perspective:
This pivotal study is the first report of a reversal agent for the direct oral anticoagulants (DOACs) in patients with clinical indications for therapy. While the number of patients is modest, there was no control arm or randomization, and the study’s primary outcome was laboratory test values instead of clinical events, the results are still important and reassuring. Unlike other DOAC reversal agents in development, idarucizumab is specific to dabigatran and cannot be used to reverse the anticoagulant affect of other medications. It remains to be seen how the anticipated availability of reversal agents, such as idarucizumab, will affect widespread use of DOACs as a class as well as dabigatran, specifically.
Keywords: Anticoagulants, Arrhythmias, Cardiac, Benzimidazoles, beta-Alanine, Blood Coagulation Tests, Endopeptidases, Hemorrhage, Hemostasis, Immunoglobulin Fragments, Secondary Prevention, Stroke, Thrombin Time
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