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
1  Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Lisa K. Jennings
2  CirQuest Labs, The University of Tennessee Health Science Center, Memphis, Tennessee, United States
,
Gerald Chi
1  Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Megan K. Yee
1  Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Rim Halaby
1  Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Tarek Nafee
1  Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Fahad AlKhalfan
1  Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Mathieu Kerneis
1  Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Serge Korjian
1  Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Yazan Daaboul
1  Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Samuel Z. Goldhaber
3  Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
,
Russel D. Hull
4  Division of Cardiology, Faculty of Medicine, University of Calgary, Alberta, Canada
,
Adrian F. Hernandez
5  Division of Cardiology, Duke University and Duke Clinical Research Institute, Durham, North Carolina, United States
,
Alexander T. Cohen
6  Department of Haematological Medicine, Guy's and St. Thomas' Hospitals, King's College London, London, United Kingdom
,
Robert A. Harrington
7  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.