title: Extended-Duration Betrixaban Reduces the Risk of Stroke Versus Standard-Dose Enoxaparin Among Hospitalized Medically Ill Patients: An APEX Trial Substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban).
abstract: Stroke is a morbid and potentially mortal complication among patients hospitalized with acute medical illness. The potential of extended-duration thromboprophylaxis with the factor Xa inhibitor betrixaban to reduce the risk of stroke compared with standard-dose enoxaparin in this population was assessed in this retrospective APEX trial substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban).
  
  
  
  Hospitalized acutely medically ill subjects (n=7513) were randomized in a double-dummy double-blind fashion to either extended-duration oral betrixaban (80 mg once daily for 35-42 days) or standard-dose subcutaneous enoxaparin (40 mg once daily for 10±4 days) for venous thromboprophylaxis. Stroke events were adjudicated by an independent, blinded event adjudication committee.
  
  
  
  The mean age of study participants was 76 years; 45% were male; 13% had had a stroke; and 45% had congestive heart failure. There were fewer all-cause strokes (0.54% versus 0.97%; relative risk [RR]=0.56; 95% confidence interval, 0.32-0.96;P=0.032; adjusted RR=0.43%; number needed to treat=233) and ischemic strokes (0.48% versus 0.91%; RR=0.53; 95% confidence interval, 0.30-0.94;P=0.026; adjusted RR=0.43%; number needed to treat=233) among patients treated with betrixaban versus enoxaparin through 77 days of follow-up. Among high-risk subjects, those with congestive heart failure or ischemic stroke as their index event, betrixaban reduced the risk of all-cause stroke (0.72% versus 1.48%; RR=0.49; 95% confidence interval, 0.26-0.90;P=0.019; adjusted RR=0.76%; number needed to treat=132) and ischemic stroke (0.63% versus 1.38%; RR=0.45; 95% confidence interval, 0.24-0.87;P=0.014; adjusted RR=0.75%; number needed to treat=134) compared with enoxaparin.
  
  
  
  Among hospitalized medically ill patients, extended-duration betrixaban significantly reduced all-cause stroke and ischemic stroke through 77 days of follow-up CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01583218.
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.). mgibson@bidmc.harvard.edu.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.).
authors.forename: Gerald
authors.initials: G
authors.lastname: Chi
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.).
authors.forename: Rim
authors.initials: R
authors.lastname: Halaby
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.).
authors.forename: Serge
authors.initials: S
authors.lastname: Korjian
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.).
authors.forename: Yazan
authors.initials: Y
authors.lastname: Daaboul
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.).
authors.forename: Purva
authors.initials: P
authors.lastname: Jain
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.).
authors.forename: Douglas
authors.initials: D
authors.lastname: Arbetter
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.).
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Goldhaber
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.).
authors.forename: Russel
authors.initials: R
authors.lastname: Hull
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.).
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.).
authors.forename: Alex
authors.initials: A
authors.lastname: Gold
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.).
authors.forename: Olga
authors.initials: O
authors.lastname: Bandman
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.).
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.affiliation: From Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (C.M.G., G.C., R. Halaby, S.K., Y.D., P.J., D.A.); Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Faculty of Medicine, Division of Cardiology, University of Calgary, AB, Canada (R. Hull); Duke University and Duke Clinical Research Institute Durham, NC (A.F.H.); Portola Pharmaceuticals Inc, South San Francisco, CA (A.G., O.B.); Department of Medicine, Stanford University, CA (R.A.H.); and Guy's and St Thomas' Hospitals, London, United Kingdom (A.T.C.).
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Cohen
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use*; D017984:Enoxaparin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy*; D054556:Venous Thromboembolism
chemical_list: D000925:Anticoagulants; D001549:Benzamides; D017984:Enoxaparin; D011725:Pyridines; C543086:betrixaban
keywords: anticoagulants; cardiology; cardiovascular diseases; intracranial hemorrhages; stroke; thrombosis