SOURCE: Glund S, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: A randomised, placebo-controlled, double-blind phase 1 trial. Lancet 2015;386:680-690.
Dabigatran (Pradaxa), rivaroxaban (Xarelto), and apixaban (Eliquis) comprise what has been recently labeled the novel oral anticoagulants (NOACs). Their use has been popularized, particularly in atrial fibrillation, due to stroke reduction that equals or surpasses that of warfarin, with less risk of cerebral hemorrhage. Drug and food interactions with warfarin, as well as the requirement for ongoing monitoring, make its use somewhat complicated. Since no monitoring and minimal drug/food interactions occur with NOACs, use is simpler.
All anticoagulant agents are associated with an increased risk of bleeding. The effects of excessive anticoagulation with warfarin may be reversed by the administration of vitamin K, or, when urgent warfarin reversal is indicated, by use of fresh frozen plasma or prothrombin complex concentrates. To date, no similar antidote to reverse the anticoagulant effects of NOACs has been available.
Idarucizumab is a monoclonal antibody to dabigatran. In this clinical dose-ranging study of idarucizumab, healthy volunteers were treated with dabigatran 220 mg twice per day and on the fourth day of dabigatran treatment, idarucizumab was administered to coincide with peak plasma levels of dabigatran.
At all idarucizumab doses of ≥ 2 g, the anticoagulant effects of dabigatran were immediately and completely reversed. Because dabigatran dissociates slowly from the dabigatran-idarucizumab complex, the reversal of anticoagulation was still fully in effect for 72 hours. No serious adverse effects were seen with idarucizumab. These results are very encouraging. A tool for reversal of NOAC anticoagulant effects may soon be available.