Introducing the Anticoagulation Antidotes

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The MD Magazine Peer Exchange “Novel Anticoagulation Options: Target-Specific Oral Agents and Their Antidotes” features leading physician specialists discussing key topics in anticoagulation therapy, including the clinical characteristics of current and emerging agents and criteria for use in specific patient populations.

This Peer Exchange is moderated by Peter Salgo, MD, professor of medicine and anesthesiology at Columbia University and an associate director of surgical intensive care at the New York-Presbyterian Hospital in New York City.

The panelists are:

• Scott Kaatz, DO, MSc, Chief Quality Officer at Hurley Medical Center in Flint, Michigan, and clinical associate professor at Michigan State University
• Seth Bilazarian, MD, clinical and interventional cardiologist at Pentucket Medical and instructor of medicine at Harvard Medical School
• Gerald Naccarelli, MD, Bernard Trabin Chair in Cardiology, professor of medicine and chief of the Division of Cardiology at Penn State University School of Medicine, and associate clinical director at Penn State Heart and Vascular Institute in Hershey, Pennsylvania
• Christian T. Ruff, MD, associate physician in the cardiovascular medicine division at Brigham and Women’s Hospital, and assistant professor of medicine at Harvard Medical School in Boston

Now that the currently available reversal options have been discussed, the panel took the time to review the basics of the investigational reversal agents, or antidotes. Andexanetalfa is a modified form of factor Xa that binds Xa, so it works for all of the Xa inhibitors (edoxaban, apixaban, rivaroxaban). Idarucizumab is a Fab fragment monoclonal antibody that binds to the direct thrombin inhibitor dabigatran, so it is a more specific antidote. Kaatz explained that, with andexanetalfa, the anti-X levels normalize immediately, but then the drug comes back in 2 or 3 hours, so the clinical trials are aiming to set a proper dosing strategy now.

PER-977 (fondaparinux) is another investigational reversal agent, and it works for all of the drugs, including heparin and enoxaparin. Naccarelli’s prediction is that the reversal agents will be approved and then they will sit untouched in the emergency room, because no one would dare use something so expensive. But its existence will add a comfort level to using the novel oral anticoagulants.