NOAC monitoring, reversal agents, and post-approval safety and effectiveness evaluation: A cardiac safety research consortium think tank.
Four non-vitamin K antagonist oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) have been approved in the United States for treatment of atrial fibrillation (AF) and venous thromboembolic disease. They have been as or more effective than the prior standards of care, with less fatal or intracranial bleeding, fewer drug and dietary interactions, and greater patient convenience. Nonetheless, the absence of the ability for clinicians to assess compliance or washout with a simple laboratory test (or to adjust dosing with a similar assessment) and the absence of an antidote to rapidly stop major hemorrhage or to enhance safety in the setting of emergent or urgent surgery/procedures have been limitations to greater non-vitamin K antagonist oral anticoagulant usage and better thromboembolic prevention. Accordingly, a Cardiac Research Safety Consortium "think tank" meeting was held in February 2015 to address these concerns. This manuscript reports on the discussions held and the conclusions reached at that meeting.
Columbia University, New York, NY. Electronic address: jar2@cumc.columbia.edu.
James A
JA
Reiffel
McMaster University and Thrombosis and Atherosclerosis Research Institute, Ontario, Canada.
Jeffrey I
JI
Weitz
Employee of Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT.
Paul
P
Reilly
Division of Hematology Products, CDER, FDA, Silver Springs, MD.
Edvardas
E
Kaminskas
Employee of Janssen Scientific Affairs, LLC, Titusville, NJ.
Troy
T
Sarich
Stanford University and Sager Consulting Experts, San Francisco, CA.
Philip
P
Sager
Employee of ACI Clinical and Lankenau Heart Institute, Wynnewood, PA.
Jonathan
J
Seltzer
D061067:Antibodies, Monoclonal, Humanized; D000931:Antidotes / Q000627:therapeutic use*; D000991:Antithrombins / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D003226:Congresses as Topic; D000069604:Dabigatran / Q000627:therapeutic use; D016903:Drug Monitoring; D015951:Factor Xa; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D006801:Humans; D010314:Partial Thromboplastin Time; D010879:Piperazines; D011358:Product Surveillance, Postmarketing; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D011994:Recombinant Proteins; D000069552:Rivaroxaban / Q000627:therapeutic use; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013844:Thiazoles / Q000627:therapeutic use; D013918:Thrombin Time; D054556:Venous Thromboembolism / Q000188:drug therapy / Q000517:prevention & control*
D061067:Antibodies, Monoclonal, Humanized; D000931:Antidotes; D000991:Antithrombins; D065427:Factor Xa Inhibitors; C580915:PRT064445; D010879:Piperazines; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D011994:Recombinant Proteins; D013844:Thiazoles; C522181:apixaban; D001120:Arginine; C000594745:idarucizumab; D000069552:Rivaroxaban; D015951:Factor Xa; D000069604:Dabigatran; C552171:edoxaban; C000593571:PER977