title: The safety and efficacy of full- versus reduced-dose betrixaban in the Acute Medically Ill VTE (Venous Thromboembolism) Prevention With Extended-Duration Betrixaban (APEX) trial.
abstract: BACKGROUND
  The APEX trial assessed the safety and efficacy of extended-duration thromboprophylaxis using betrixaban versus standard dosing of enoxaparin among hospitalized, acutely ill medical patients. The 80-mg betrixaban dose was halved to 40 mg among subjects with severe renal insufficiency and those receiving a concomitant strong P-glycoprotein inhibitor.
  
  
  METHODS
  This analysis assessed the pharmacokinetics, efficacy, and safety of full- (80 mg) and reduced-dose (40 mg) betrixaban relative to enoxaparin in the APEX trial.
  
  
  RESULTS
  The median concentration of betrixaban among subjects administered the 80-mg dose was higher than that of the 40-mg dose (19 ng/mL vs 11 ng/mL, P<.001). In the primary analysis cohort 1 (d-dimer ≥2× upper limit of normal), the primary efficacy outcome (asymptomatic proximal deep vein thrombosis, symptomatic proximal or distal deep vein thrombosis, symptomatic nonfatal pulmonary embolism, or venous thromboembolism-related death) was significantly reduced among subjects treated with 80 mg of extended-duration betrixaban versus enoxaparin (6.27% [95/1516] vs 8.39% [130/1549], relative risk reduction=0.26 [0.04-0.42], P=.023), and similarly in the entire primary efficacy outcome population (4.87% [122/2506] vs 7.06% [181/2562], relative risk reduction=0.30 [0.13-0.44], P=.001). There was no difference in the primary outcome for subjects treated with 40 mg betrixaban vs enoxaparin across cohorts. In addition, there was no excess of major bleeding associated with either betrixaban dose compared with enoxaparin.
  
  
  CONCLUSIONS
  The 80-mg betrixaban dose achieves higher plasma concentrations than the 40-mg dose and, in contrast to the 40-mg dose, is associated with improved efficacy across all cohorts relative to standard-dose enoxaparin without an excess risk of major bleeding in the management of medically ill subjects.
authors.affiliation: Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Electronic address: mgibson@bidmc.harvard.edu.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.affiliation: Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Rim
authors.initials: R
authors.lastname: Halaby
authors.affiliation: Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Serge
authors.initials: S
authors.lastname: Korjian
authors.affiliation: Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Yazan
authors.initials: Y
authors.lastname: Daaboul
authors.affiliation: Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Arbetter
authors.affiliation: Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Megan K
authors.initials: MK
authors.lastname: Yee
authors.affiliation: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Goldhaber
authors.affiliation: RAH Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: Russel
authors.initials: R
authors.lastname: Hull
authors.affiliation: Division of Cardiology, Duke University and Duke Clinical Research Institute, Durham, NC.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: Portola Pharmaceuticals Inc, South San Francisco, CA.
authors.forename: Shiao-Ping
authors.initials: SP
authors.lastname: Lu
authors.affiliation: Portola Pharmaceuticals Inc, South San Francisco, CA.
authors.forename: Olga
authors.initials: O
authors.lastname: Bandman
authors.affiliation: Portola Pharmaceuticals Inc, South San Francisco, CA.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Leeds
authors.affiliation: Portola Pharmaceuticals Inc, South San Francisco, CA.
authors.forename: Alex
authors.initials: A
authors.lastname: Gold
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.affiliation: Guy's and St Thomas' Hospitals, London, UK.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Cohen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D001549:Benzamides / Q000008:administration & dosage*; D004311:Double-Blind Method; D017984:Enoxaparin / Q000627:therapeutic use; D065427:Factor Xa Inhibitors / Q000008:administration & dosage*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006760:Hospitalization; D006801:Humans; D008297:Male; D011655:Pulmonary Embolism / Q000517:prevention & control*; D011725:Pyridines / Q000008:administration & dosage*; D054556:Venous Thromboembolism / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D001549:Benzamides; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D011725:Pyridines; C543086:betrixaban