CC-BY 4.0 · TH Open 2018; 02(01): e16-e24
DOI: 10.1055/s-0037-1615288
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Association of D-dimer Levels with Clinical Event Rates and the Efficacy of Betrixaban versus Enoxaparin in the APEX Trial

C. Michael Gibson
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Lisa K. Jennings
CirQuest Labs, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
,
Gerald Chi
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Megan K. Yee
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Rim Halaby
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Tarek Nafee
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Fahad AlKhalfan
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Mathieu Kerneis
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Serge Korjian
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Yazan Daaboul
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Samuel Z. Goldhaber
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Russel D. Hull
Division of Cardiology, Faculty of Medicine, University of Calgary, Alberta, Canada
,
Adrian F. Hernandez
Division of Cardiology, Duke University and Duke Clinical Research Institute, Durham, North Carolina, United States
,
Alexander T. Cohen
Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College London, London, United Kingdom
,
Robert A. Harrington
Department of Medicine, Stanford University, Stanford, California, United States
› Author Affiliations
Further Information

Publication History

05 September 2017

20 November 2017

Publication Date:
08 January 2018 (online)

Abstract

Background Elevated D-dimer concentrations are associated with an increased risk of venous thromboembolism (VTE). However, they may also provide prognostic value. The present analysis sought to study the association of D-dimer levels with VTE event rates and the efficacy of betrixaban versus enoxaparin in the APEX trial.

Methods Hospitalized acutely medically ill subjects (n = 7,513) 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. D-dimer was assessed using a central core laboratory measurement.

Results For every 0.25 µg/mL increase in D-dimer concentration, there was a 2% increase in the relative risk of experiencing the primary efficacy endpoint (asymptomatic deep vein thrombosis [DVT], symptomatic DVT, nonfatal pulmonary embolism, or VTE-related death) in both the betrixaban (p < 0.001) and enoxaparin (p < 0.001) treatment arms. Among D-dimer-positive (≥ 2 × upper limit of normal; corresponding to ≥ 1.00 µg/mL) subjects, extended-duration betrixaban reduced the risk of experiencing the primary efficacy outcome (5.4% [n = 124] vs. 7.6% [n = 170]; odds ratio = 0.69; 95% confidence interval: 0.55–0.88; absolute risk reduction = 2.2%, number needed to treat = 46, p = 0.003). There was no interaction between D-dimer and the treatment effect (p int = 0.53).

Conclusion Extended-duration betrixaban was superior to standard-duration enoxaparin, irrespective of D-dimer level at baseline. To prevent one VTE event, 46 D-dimer-positive patients would need to be treated with betrixaban.