Request to Join
has invited you to join this group
-
Authors
-
Leo Pharma Chair in Thromboembolism Research, McMaster UniversityMark Crowther, MD, MSc, FRCPC
Leo Pharma Chair in Thromboembolism Research, McMaster UniversityLeo Pharma Chair in Thromboembolism Research, McMaster University
-
Experts
-
Executive Director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart & Vascular CenterDeepak Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC
Executive Director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart & Vascular CenterExecutive Director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart & Vascular Center
-
Investigator, TIMI Study Group, Cardiovascular Division, Brigham and Women’s HospitalChristian Ruff, MD, MPH
Investigator, TIMI Study Group, Cardiovascular Division, Brigham and Women’s HospitalInvestigator, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital
-
Professor of Medicine at Uniformed Services University of the Health SciencesLisa Moores, MD, FCCP
Professor of Medicine at Uniformed Services University of the Health SciencesProfessor of Medicine at Uniformed Services University of the Health Sciences
-
Executive Director, Thrombosis and Atherosclerosis Research InstituteJeffrey Weitz, MD, FRCP(C), FACP, FCCP, FAHA, FACC, FESC, FCAHS
Executive Director, Thrombosis and Atherosclerosis Research InstituteExecutive Director, Thrombosis and Atherosclerosis Research Institute
-
Head of the Thrombosis Research Unit, Center for Vascular Medicine, University Hospital DresdenJan Beyer-Westendorf, MD
Head of the Thrombosis Research Unit, Center for Vascular Medicine, University Hospital DresdenHead of the Thrombosis Research Unit, Center for Vascular Medicine, University Hospital Dresden
-
Professor of Cardiovascular Medicine at University of BirminghamGregory Lip, MD, FRCP, DFM, FACC, FESC
Professor of Cardiovascular Medicine at University of BirminghamProfessor of Cardiovascular Medicine at University of Birmingham
-
Professor of Medicine at Hofstra North Shore - LIJ School of MedicineJack Ansell, MD, MACP
Professor of Medicine at Hofstra North Shore - LIJ School of MedicineProfessor of Medicine at Hofstra North Shore - LIJ School of Medicine
-
Associate Chair, Emergency Medicine, Baylor College of MedicineFrank Peacock, MD, FACEP
Associate Chair, Emergency Medicine, Baylor College of MedicineAssociate Chair, Emergency Medicine, Baylor College of Medicine
-
Director of the Cardiac Care Unit, Duke University Medical CenterChristopher Granger, MD
Director of the Cardiac Care Unit, Duke University Medical CenterDirector of the Cardiac Care Unit, Duke University Medical Center
-
Hematologist at Brigham and Women's Hospital and Dana Farber Cancer InstituteJean Connors, MD
Hematologist at Brigham and Women's Hospital and Dana Farber Cancer InstituteHematologist at Brigham and Women's Hospital and Dana Farber Cancer Institute
-
Head of Atherothrombosis, Inflammation, and Platelets; University of FreiburgIngo Ahrens, MD
Head of Atherothrombosis, Inflammation, and Platelets; University of FreiburgHead of Atherothrombosis, Inflammation, and Platelets; University of Freiburg
-
Medical Education and Scientific Support at Boehringer IngelheimDr. Joanne van Ryn
Medical Education and Scientific Support at Boehringer IngelheimMedical Education and Scientific Support at Boehringer Ingelheim
-
Executive Vice President of Clinical and Medical Affairs at PerosphereJames Costin, MD
Executive Vice President of Clinical and Medical Affairs at PerosphereExecutive Vice President of Clinical and Medical Affairs at Perosphere
-
Director of Cardiac Catheterization Laboratories & Interventional Cardiology Guthrie Health Services at Guthrie Health Systems Robert Packer HospitalEdo Kaluski, MD
Director of Cardiac Catheterization Laboratories & Interventional Cardiology Guthrie Health Services at Guthrie Health Systems Robert Packer HospitalDirector of Cardiac Catheterization Laboratories & Interventional Cardiology Guthrie Health Services at Guthrie Health Systems Robert Packer Hospital
-
Professor of Surgery and Director, Surgical Critical Care and Trauma Surgery Fellowships at The University of Texas Health Science Center at HoustonBryan Cotton, MD, MPH
Professor of Surgery and Director, Surgical Critical Care and Trauma Surgery Fellowships at The University of Texas Health Science Center at HoustonProfessor of Surgery and Director, Surgical Critical Care and Trauma Surgery Fellowships at The University of Texas Health Science Center at Houston
-
Cardiologist at Royal Brompton Hospital and Imperial College LondonVassilios Vassiliou, MA, MD, FESC
Cardiologist at Royal Brompton Hospital and Imperial College LondonCardiologist at Royal Brompton Hospital and Imperial College London
-
Director of the Institute of Cardiology at "G. d'Annunzio" University, ChietiRaffaele De Caterina, MD, PhD, FESC
Director of the Institute of Cardiology at "G. d'Annunzio" University, ChietiDirector of the Institute of Cardiology at "G. d'Annunzio" University, Chieti
-
Lead Moderators
-
Hematology-Oncology Fellow at Boston Medical CenterChris Dittus, DO, MPH
Hematology-Oncology Fellow at Boston Medical CenterHematology-Oncology Fellow at Boston Medical Center
About the Discussion
@NEJM Ask the Authors & Experts: Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity
Original Article
Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity
Background
Bleeding is a complication of treatment with factor Xa inhibitors, but there are no specific agents for the reversal of the effects of these drugs. Andexanet is designed to reverse the anticoagulant effects of factor Xa inhibitors.
Methods
Healthy older volunteers were given 5 mg of apixaban twice daily or 20 mg of rivaroxaban daily. For each factor Xa inhibitor, a two-part randomized placebo-controlled study was conducted to evaluate andexanet administered as a bolus or as a bolus plus a 2-hour infusion. The primary outcome was the mean percent change in anti–factor Xa activity, which is a measure of factor Xa inhibition by the anticoagulant.
Results
Among the apixaban-treated participants, anti–factor Xa activity was reduced by 94% among those who received an andexanet bolus (24 participants), as compared with 21% among those who received placebo (9 participants) (P<0.001), and unbound apixaban concentration was reduced by 9.3 ng per milliliter versus 1.9 ng per milliliter (P<0.001); thrombin generation was fully restored in 100% versus 11% of the participants (P<0.001) within 2 to 5 minutes. Among the rivaroxaban-treated participants, anti–factor Xa activity was reduced by 92% among those who received an andexanet bolus (27 participants), as compared with 18% among those who received placebo (14 participants) (P<0.001), and unbound rivaroxaban concentration was reduced by 23.4 ng per milliliter versus 4.2 ng per milliliter (P<0.001); thrombin generation was fully restored in 96% versus 7% of the participants (P<0.001). These effects were sustained when andexanet was administered as a bolus plus an infusion. In a subgroup of participants, transient increases in levels of d-dimer and prothrombin fragments 1 and 2 were observed, which resolved within 24 to 72 hours. No serious adverse or thrombotic events were reported.
Conclusions
Andexanet reversed the anticoagulant activity of apixaban and rivaroxaban in older healthy participants within minutes after administration and for the duration of infusion, without evidence of clinical toxic effects. (Funded by Portola Pharmaceuticals and others; ANNEXA-A and ANNEXA-R ClinicalTrials.gov numbers NCT02207725 and NCT02220725.)
-
Authors
-
Leo Pharma Chair in Thromboembolism Research, McMaster UniversityMark Crowther, MD, MSc, FRCPC
Leo Pharma Chair in Thromboembolism Research, McMaster University
Leo Pharma Chair in Thromboembolism Research, McMaster University
-
Experts
-
Executive Director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart & Vascular CenterDeepak Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC
Executive Director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart & Vascular Center
Executive Director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart & Vascular Center
-
Investigator, TIMI Study Group, Cardiovascular Division, Brigham and Women’s HospitalChristian Ruff, MD, MPH
Investigator, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital
Investigator, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital
-
Professor of Medicine at Uniformed Services University of the Health SciencesLisa Moores, MD, FCCP
Professor of Medicine at Uniformed Services University of the Health Sciences
Professor of Medicine at Uniformed Services University of the Health Sciences
-
Executive Director, Thrombosis and Atherosclerosis Research InstituteJeffrey Weitz, MD, FRCP(C), FACP, FCCP, FAHA, FACC, FESC, FCAHS
Executive Director, Thrombosis and Atherosclerosis Research Institute
Executive Director, Thrombosis and Atherosclerosis Research Institute
-
Head of the Thrombosis Research Unit, Center for Vascular Medicine, University Hospital DresdenJan Beyer-Westendorf, MD
Head of the Thrombosis Research Unit, Center for Vascular Medicine, University Hospital Dresden
Head of the Thrombosis Research Unit, Center for Vascular Medicine, University Hospital Dresden
-
Professor of Cardiovascular Medicine at University of BirminghamGregory Lip, MD, FRCP, DFM, FACC, FESC
Professor of Cardiovascular Medicine at University of Birmingham
Professor of Cardiovascular Medicine at University of Birmingham
-
Professor of Medicine at Hofstra North Shore - LIJ School of MedicineJack Ansell, MD, MACP
Professor of Medicine at Hofstra North Shore - LIJ School of Medicine
Professor of Medicine at Hofstra North Shore - LIJ School of Medicine
-
Associate Chair, Emergency Medicine, Baylor College of MedicineFrank Peacock, MD, FACEP
Associate Chair, Emergency Medicine, Baylor College of Medicine
Associate Chair, Emergency Medicine, Baylor College of Medicine
-
Director of the Cardiac Care Unit, Duke University Medical CenterChristopher Granger, MD
Director of the Cardiac Care Unit, Duke University Medical Center
Director of the Cardiac Care Unit, Duke University Medical Center
-
Hematologist at Brigham and Women's Hospital and Dana Farber Cancer InstituteJean Connors, MD
Hematologist at Brigham and Women's Hospital and Dana Farber Cancer Institute
Hematologist at Brigham and Women's Hospital and Dana Farber Cancer Institute
-
Head of Atherothrombosis, Inflammation, and Platelets; University of FreiburgIngo Ahrens, MD
Head of Atherothrombosis, Inflammation, and Platelets; University of Freiburg
Head of Atherothrombosis, Inflammation, and Platelets; University of Freiburg
-
Medical Education and Scientific Support at Boehringer IngelheimDr. Joanne van Ryn
Medical Education and Scientific Support at Boehringer Ingelheim
Medical Education and Scientific Support at Boehringer Ingelheim
-
Executive Vice President of Clinical and Medical Affairs at PerosphereJames Costin, MD
Executive Vice President of Clinical and Medical Affairs at Perosphere
Executive Vice President of Clinical and Medical Affairs at Perosphere
-
Director of Cardiac Catheterization Laboratories & Interventional Cardiology Guthrie Health Services at Guthrie Health Systems Robert Packer HospitalEdo Kaluski, MD
Director of Cardiac Catheterization Laboratories & Interventional Cardiology Guthrie Health Services at Guthrie Health Systems Robert Packer Hospital
Director of Cardiac Catheterization Laboratories & Interventional Cardiology Guthrie Health Services at Guthrie Health Systems Robert Packer Hospital
-
Professor of Surgery and Director, Surgical Critical Care and Trauma Surgery Fellowships at The University of Texas Health Science Center at HoustonBryan Cotton, MD, MPH
Professor of Surgery and Director, Surgical Critical Care and Trauma Surgery Fellowships at The University of Texas Health Science Center at Houston
Professor of Surgery and Director, Surgical Critical Care and Trauma Surgery Fellowships at The University of Texas Health Science Center at Houston
-
Cardiologist at Royal Brompton Hospital and Imperial College LondonVassilios Vassiliou, MA, MD, FESC
Cardiologist at Royal Brompton Hospital and Imperial College London
Cardiologist at Royal Brompton Hospital and Imperial College London
-
Director of the Institute of Cardiology at "G. d'Annunzio" University, ChietiRaffaele De Caterina, MD, PhD, FESC
Director of the Institute of Cardiology at "G. d'Annunzio" University, Chieti
Director of the Institute of Cardiology at "G. d'Annunzio" University, Chieti
-
Lead Moderators
-
Hematology-Oncology Fellow at Boston Medical CenterChris Dittus, DO, MPH
Hematology-Oncology Fellow at Boston Medical Center
Hematology-Oncology Fellow at Boston Medical Center
