Open Access
CC BY 4.0 · TH Open 2019; 03(02): e103-e108
DOI: 10.1055/s-0039-1685496
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Characterization of Major and Clinically Relevant Non-Major Bleeds in the APEX Trial

Authors

  • Megan K. Yee

    1   Boston Clinical Research Institute, Newton, Massachusetts, United States
  • C. Michael Gibson

    1   Boston Clinical Research Institute, Newton, Massachusetts, United States
  • Tarek Nafee

    1   Boston Clinical Research Institute, Newton, Massachusetts, United States
  • Mathieu Kerneis

    2   PERFUSE Study Group, Division of Cardiovascular, Departments of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
  • Yazan Daaboul

    2   PERFUSE Study Group, Division of Cardiovascular, Departments of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
  • Serge Korjian

    2   PERFUSE Study Group, Division of Cardiovascular, Departments of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
  • Gerald Chi

    2   PERFUSE Study Group, Division of Cardiovascular, Departments of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
  • Fahad AlKhalfan

    2   PERFUSE Study Group, Division of Cardiovascular, Departments of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
  • Adrian F. Hernandez

    3   Duke University and Duke Clinical Research Institute, Durham, North Carolina, United States
  • Russell D. Hull

    4   Division of Cardiology, R.A.H. Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
  • Alexander T. Cohen

    5   Department of Haematological Medicine, Guy's and St Thomas' Hospitals, London, United Kingdom
  • Samuel Z. Goldhaber

    6   Division of Cardiovascular, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States

Funding This study was funded by Portola Pharmaceuticals, Inc.
Further Information

Publication History

20 December 2018

25 February 2019

Publication Date:
17 April 2019 (online)

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Abstract

Background Among medically ill patients treated with thromboprophylaxis, betrixaban was not associated with an increase in major bleeding compared with enoxaparin, but an increase in clinically relevant non-major (CRNM) bleeding was observed. The aim of this analysis is to describe the severity and clinical consequences of major and CRNM bleeding in the APEX trial.

Methods The APEX trial randomized 7,513 hospitalized acutely ill medical patients to receive either enoxaparin for 6 to 14 days or betrixaban for 35 to 42 days. Subjects receiving a concomitant strong p-glycoprotein inhibitor or with creatinine clearance <30 mL/min were administered a reduced dose of study drug.

Results A total of 25 (0.7%) and 21 (0.6%) major bleeds occurred in the betrixaban and enoxaparin arms, respectively (p = NS) and a total of 91 (2.5%) and 38 (1.0%) CRNM bleeds occurred in the betrixaban and enoxaparin arm (p < 0.001), respectively. Most major bleeds were considered moderate or severe and most CRNM bleeds were considered mild and moderate (p = NS). One fatal major bleed occurred in each treatment arm. Rates of major or CRNM bleeds resulting in new or prolonged hospitalization (major: 44.0 vs. 28.6%; CRNM: 12.1 vs. 21.1%) or study treatment interruption or cessation (major: 72.0 vs. 71.4%; CRNM: 71.3 vs. 68.4%) were similar between treatment arms (p = NS).

Conclusions In the APEX trial, CRNM bleeds were mild or moderate in nature and had less of a clinical impact than major bleeds. The severity and clinical sequela of bleeds in the betrixaban arm were comparable to those in the enoxaparin arm.

Clinical Trial Registration URL: http://www.clinicaltrials.gov.; Unique identifier: NCT01583218.

Supplementary Material