Anticoagulation reversal in the era of the non-vitamin K oral anticoagulants

Europace. 2016 Jul;18(7):955-64. doi: 10.1093/europace/euv030. Epub 2015 Mar 26.


In recent years, non-vitamin K oral anticoagulants (NOACs) have emerged as an alternative to warfarin for the prevention and treatment of thrombo-embolic disease. Large randomized trials have demonstrated that these agents, which act by directly targeting thrombin (dabigatran) and factor Xa (rivaroxaban, apixaban, and edoxaban), are at least as effective as warfarin, with lower rates of bleeding and fewer interactions with food and drugs. In addition, NOACs have a more predictable anticoagulant effect, allowing a fixed dose regimen and obviating the need for routine anticoagulation monitoring. Since the introduction of NOACs, one of the major concerns for clinicians has been the lack of specific agents to reverse their anticoagulant effect in case of life-threatening haemorrhagic complications or emergency surgery, which have limited their use in patients deemed at a higher risk of bleeding. New specific antidotes (e.g. idarucizumab, andexanet alfa, and ciraparantag) show promising data, and may soon become available for clinical use. In this article, we review the pharmacology of these agents, the incidence and outcomes of haemorrhagic complications, the available strategies for anticoagulation reversal, and the more recent advances for the development of specific antidotes.

Keywords: Andexanet alfa; Anticoagulation; Antidote; Apixaban; Bleeding; Ciraparantag; Dabigatran; Edoxaban; Idarucizumab; Non-vitamin K oral anticoagulants; Reversal; Rivaroxaban; Warfarin.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Antithrombins / adverse effects
  • Antithrombins / therapeutic use*
  • Blood Coagulation / drug effects
  • Factor Xa Inhibitors / adverse effects
  • Factor Xa Inhibitors / therapeutic use*
  • Hemorrhage / chemically induced*
  • Humans
  • Randomized Controlled Trials as Topic
  • Thromboembolism / drug therapy*


  • Anticoagulants
  • Antithrombins
  • Factor Xa Inhibitors