Reversing anticoagulant effects of novel oral anticoagulants: role of ciraparantag, andexanet alfa, and idarucizumab

Vasc Health Risk Manag. 2016 Feb 17:12:35-44. doi: 10.2147/VHRM.S89130. eCollection 2016.

Abstract

Novel oral anticoagulants (NOACs) are increasingly used in clinical practice, but lack of commercially available reversal agents is a major barrier for mainstream use of these therapies. Specific antidotes to NOACs are under development. Idarucizumab (aDabi-Fab, BI 655075) is a novel humanized mouse monoclonal antibody that binds dabigatran and reverses its anticoagulant effect. In a recent Phase III study (Reversal Effects of Idarucizumab on Active Dabigatran), a 5 g intravenous infusion of idarucizumab resulted in the normalization of dilute thrombin time in 98% and 93% of the two groups studied, with normalization of ecarin-clotting time in 89% and 88% patients. Two other antidotes, andexanet alfa (PRT064445) and ciraparantag (PER977) are also under development for reversal of NOACs. In this review, we discuss commonly encountered management issues with NOACs such as periprocedural management, laboratory monitoring of anticoagulation, and management of bleeding. We review currently available data regarding specific antidotes to NOACs with respect to pharmacology and clinical trials.

Keywords: dabigatran; idarucizumab; novel oral anticoagulant; reversal.

Publication types

  • Review
  • Video-Audio Media

MeSH terms

  • Administration, Oral
  • Animals
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Anticoagulants / pharmacokinetics
  • Antidotes / adverse effects
  • Antidotes / therapeutic use*
  • Arginine / adverse effects
  • Arginine / analogs & derivatives*
  • Arginine / therapeutic use
  • Blood Coagulation / drug effects*
  • Blood Coagulation Tests
  • Coagulants / adverse effects
  • Coagulants / therapeutic use*
  • Drug Monitoring / methods
  • Factor Xa / adverse effects
  • Factor Xa / therapeutic use*
  • Hemorrhage / chemically induced
  • Hemorrhage / drug therapy*
  • Humans
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use*

Substances

  • Antibodies, Monoclonal, Humanized
  • Anticoagulants
  • Antidotes
  • Coagulants
  • PRT064445
  • Piperazines
  • Recombinant Proteins
  • Arginine
  • idarucizumab
  • Factor Xa
  • PER977