The direct oral
anticoagulants (DOACs) provide a number of clinical advantages over
vitamin K antagonists for the treatment of
thromboembolism, including improved efficacy and safety, as well as no need for regular monitoring of
anticoagulant effect. However, as with all
anticoagulants,
bleeding complications may occur, and
anticoagulant reversal may be required in specific clinical situations, such as in patients experiencing spontaneous or traumatic bleeds, or in anticoagulated patients requiring emergency surgery or other invasive procedures. Therefore, several reversal agents for the DOACs are in development. This includes the specific reversal agent
idarucizumab, which has been approved by the U.S. Food and Drug Administration and the European Medicines Agency for use in patients treated with
dabigatran when urgent reversal of its
anticoagulant effects is needed.
Idarucizumab is a humanized
monoclonal antibody fragment that binds with high affinity to free and
thrombin-bound
dabigatran, resulting in an almost irreversibly bound
idarucizumab-
dabigatran complex and thereby neutralizing
dabigatran's
anticoagulant activity. The reversal of the
anticoagulant effects of
dabigatran by
idarucizumab has been demonstrated in animal
bleeding models, in healthy volunteers with a range of ages and renal function, and in anticoagulated patients. In the phase 1 trials, at doses of 2 g or greater,
idarucizumab resulted in immediate and complete reversal of the
dabigatran anticoagulant effects and was well tolerated. In the absence of
dabigatran,
idarucizumab showed no effect on coagulation parameters or
thrombin formation. These findings provide initial evidence that
idarucizumab could provide a safe and effective means of reversing
anticoagulant activity in patients treated with
dabigatran in need of emergency surgery or in emergency
bleeding situations.