In emergency settings, rapid reversal of the anticoagulant effect of dabigatran is critical to patient management. The RE-VERSE AD study assessed the efficacy of idarucizumab to reverse anticoagulation in patients receiving dabigatran who had serious, uncontrolled bleeding or who required urgent surgery/intervention. This is the first clinical trial testing a specific reversal agent that has completed full enrollment.
- Idarucizumab was found to rapidly, durably, and safely reverse the anticoagulant effect of dabigatran.
- Median time to cessation of bleeding in evaluable patients without intracranial bleeding: 2.5 hours.
- There were no adverse safety signals identified during the study.
Charles Pollack, M.D. presented the findings from the RE-VERSE AD study at Tuesday’s Late-Breaking Abstract Session. Idarucizumab, a monoclonal antibody fragment, was developed to reverse dabigatran anticoagulation. This multicenter, prospective, open-label study, tested the utility of 5 g of intravenous idarucizumab in reversing dabigatran anticoagulation in two patient groups:
- Patients with serious, uncontrolled bleeding (Group A);
- Patients requiring urgent surgery or intervention (Group B).
The primary endpoint was maximum reversal of dabigatran anticoagulation within 4 hours of idarucizumab administration as determined by the dilute thrombin time or ecarin clotting time. Secondary endpoints included restoration of hemostasis and safety evaluations.
A total of 503 patients were enrolled, 301 in Group A and 202 in Group B. Median maximal reversal of dabigatran at 4 hours was 100% (95% confidence interval, 100% to 100%) as determined by either clotting assay. Among patients in Group A, 137 (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) with intracranial hemorrhage. The median time to cessation of bleeding in evaluable patients without intracranial bleeding was 2.5 hours. The median time to surgery or procedure in Group B patients was 1.6 hours, and peri-procedural hemostasis was assessed as normal in 93.4%, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. Mortality at 90 days was 18.8% and 18.9% in Groups A and B, respectively. At 90 days, thromboembolic events had occurred in 6.7% of Group A, and 9.0% of Group B patients. There were no adverse safety signals.
In emergency settings, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran.