Effects of Idarucizumab on Intracranial Bleeding in Dabigatran-Treated Patients

Whether the dabigatran reversal agent idarucizumab improves clinical outcomes in dabigatran-treated patients with intracranial hemorrhage (ICH) is being addressed in the RE-VERSE AD study. Initial results were presented at the 2016 International Stroke Conference in Los Angeles.

“Our results show that idarucizumab rapidly reverses the anticoagulant effect of dabigatran in patients with intracranial bleeding,” Richard A. Bernstein MD, PhD, of Northwestern Memorial Hospital in Chicago, told Cardiology Advisor. The study provides the first data on clinical outcomes for idarucizumab’s use in dabigatran-treated patients who present with ICH.   

Dr Bernstein and colleagues evaluated the effects of idarucizumab on coagulation, imaging studies, and clinical outcomes in 18 patients with ICH included in an interim analysis of 90 patients. In this ongoing, open-label, phase 3 cohort study, patients taking dabigatran who presented with ICH were treated with idarucizumab 5 g, administered as 2 separate 2.5 g intravenous bolus infusions no more than 15 minutes apart. Maximum reversal of dabigatran’s anticoagulant effect, measured by dilute thrombin time or ecarin clotting time determined by a central laboratory, was the study’s primary end point.¹

The mortality rate associated with ICH in patients receiving anticoagulation remains high, even with today’s growing selection of anticoagulant drugs. In the RE-LY trial that compared dabigatran and warfarin in patients with atrial fibrillation, dabigatran was associated with a significantly lower annualized rate of ICH than warfarin.² Dabigatran is a non-vitamin K oral anticoagulant (NOAC) approved for the prevention of stroke in individuals with nonvalvular atrial fibrillation.

Idarucizumab, which was approved in October 2015, is a humanized Fab fragment directed against dabigatran and the first specific NOAC reversal agent to be approved. Last year, RE-VERSE AD study investigator C. V. Pollock Jr and colleagues reported that idarucizumab reversed the anticoagulant effect of dabigatran completely within minutes in patients with serious bleeding and in individuals who required anticoagulation reversal before an urgent procedure.³

More ISC 2016 coverage here.

References

1. Bernstein RA, Pollack Jr CV, Weitz JI, et al. Abstract 213. Effect of idarucizumab on intracranial bleeding in dabigatran-treated patients: initial results from RE-VERSE AD. Presented at the International Stroke Conference 2016; February 17-19, 2016; Los Angeles, CA.
2. Connolly SJ, Ezekowitz MD, Yusuf S, et al; for the RE-LY Steering Committee and Investigators. Dabigatran vs warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-1151. doi: 10.1056/NEJMoa0905561.
3. Pollock CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015;373(6):511-520. doi: 10.1056/NEJMoa1502000.