Direct oral anticoagulants: a review on the current role and scope of reversal agents

  • Rahul ChaudharyEmail author
  • Tushar Sharma
  • Jalaj Garg
  • Ajaypaul Sukhi
  • Kevin Bliden
  • Udaya Tantry
  • Mohit Turagam
  • Dhanunjaya Lakkireddy
  • Paul Gurbel


New guideline recommendations prefer direct oral anticoagulants (DOACs) over warfarin in DOAC-eligible patients with atrial fibrillation and patients with venous thromboembolism. As expected with all antithrombotic agents, there is an associated increased risk of bleeding complications in patients receiving DOACs that can be attributed to the DOAC itself, or other issues such as acute trauma, invasive procedures, or underlying comorbidities. For the majority of severe bleeding events, the widespread approach is to withdraw the DOAC, then provide supportive measures and “watchful waiting” with the expectation that the bleeding event will resolve with time. However, urgent reversal of anticoagulation may be advantageous in patients with serious or life-threatening bleeding or in those requiring urgent surgery or procedures. Until recently, the lack of specific reversal agents, has affected the uptake of these agents in clinical practice despite a safer profile compared to warfarin in clinical trials. In cases of life-threatening or uncontrolled bleeding or when patients require emergency surgery or urgent procedures, idarucizumab has been recently approved for reversal of anticoagulation in dabigatran-treated patients and andexanet alfa for factor Xa inhibitor-treated treated patients. The current review summarizes the current clinical evidence and scope of these agents with the potential impact on DOAC use in clinical practice.


DOACs Andexanet alfa Apixaban Dabigatran Edoxaban Betrixaban Idarucizumab Reversal Rivaroxaban 


Author contributions

RC—Concept and design; analysis and interpretation of data; revising the intellectual content; and final approval of the version to be published. TS—Critical writing; and final approval of the version to be published. JG—Analysis and interpretation of data; critical writing with revision of intellectual content; and final approval of the version to be published. AS—Interpretation of data; revising the intellectual content; and final approval of the version to be published. KB—Concept and design; analysis and interpretation of data; revising the intellectual content; and final approval of the version to be published. UT—Interpretation of data; revising the intellectual content; and final approval of the version to be published. MT—Concept and design; revising the intellectual content; and final approval of the version to be published. DL—Concept and design; revising the intellectual content; and final approval of the version to be published. PG—Concept and design; interpretation of data; revising the intellectual content; and final approval of the version to be published.

Compliance with ethical standards

Conflict of interest

Paul Gurbel reports serving as a consultant for Daiichi Sankyo/Lilly, Bayer, AstraZeneca, Accumetrics, Merck, Medtronic, Janssen, CSL, and Haemonetics; receiving grants from the National Institutes of Health, Daiichi Sankyo, Lilly, CSL, AstraZeneca, Haemonetics, Harvard Clinical Research Institute, and Duke Clinical Research Institute; receiving payment for lectures, including service on speakers’ bureaus, from Lilly, Daiichi Sankyo, and Merck; receiving payment for development of educational presentations from Merck, the Discovery Channel, and Pri-Med; Dr. Gurbel is holding stock or stock options in Merck, Medtronic, and Pfizer; and holding patents in the area of personalized antiplatelet therapy and interventional cardiology. No other authors report any potential conflicts of interest.

Ethical approval

An approval by an ethics committee was not applicable.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Hospital Internal MedicineMayo ClinicRochesterUSA
  2. 2.Indiana University BloomingtonBloomingtonUSA
  3. 3.Sinai Hospital of BaltimoreBaltimoreUSA
  4. 4.Medical College of WisconsinMilwaukeeUSA
  5. 5.Inova Center for Thrombosis Research and Drug DevelopmentInova Heart and Vascular InstituteFalls ChurchUSA
  6. 6.Helmsley Electrophysiology Center in the Department of Cardiology and Icahn School of Medicine at Mount SinaiNew YorkUSA
  7. 7.University of Kansas, Medical CenterKansas CityUSA

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