Thromb Haemost 2018; 118(12): 2046-2052
DOI: 10.1055/s-0038-1675606
Coagulation and Fibrinolysis
Georg Thieme Verlag KG Stuttgart · New York

Asymptomatic Deep Vein Thrombosis is Associated with an Increased Risk of Death: Insights from the APEX Trial

Arzu Kalayci
1  Division of Cardiovascular, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
C. Michael Gibson
1  Division of Cardiovascular, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Gerald Chi
1  Division of Cardiovascular, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Megan K. Yee
1  Division of Cardiovascular, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Serge Korjian
1  Division of Cardiovascular, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Sudarshana Datta
1  Division of Cardiovascular, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Tarek Nafee
1  Division of Cardiovascular, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Mike Gurin
1  Division of Cardiovascular, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Noah Haroian
1  Division of Cardiovascular, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Iqra Qamar
1  Division of Cardiovascular, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
,
Russell D. Hull
2  Division of Cardiology, R.A.H Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
,
Adrian F. Hernandez
3  Duke Clinical Research Institute, Durham, North Carolina, United States
,
Alexander T. Cohen
4  Department of Haematological Medicine, Guy's and St Thomas' Hospitals, King's College, London, United Kingdom
,
Robert A. Harrington
5  Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, California, United States
,
Samuel Z. Goldhaber
6  Division of Cardiovascular, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
› Author Affiliations
Funding This study was funded by Portola Pharmaceuticals Inc.

Clinical Trial Registration ClinicalTrials.gov identifier: NCT01583218 (http://www.clinicaltrials.gov).
Further Information

Publication History

15 March 2018

29 September 2018

Publication Date:
12 November 2018 (eFirst)

Abstract

Aim Asymptomatic deep vein thrombosis (DVT) diagnosed with compression ultrasound (CUS) is a common endpoint in trials assessing the efficacy of anticoagulants to prevent venous thromboembolism (VTE), but the relationship of asymptomatic thrombus to mortality remains uncertain.

Methods In the APEX trial (ClinicalTrials.gov: NCT01583218), 7,513 acutely ill hospitalized medical patients were randomly assigned to extended-duration betrixaban (35–42 days) or enoxaparin (10 ± 4 days). Asymptomatic DVT was assessed once with CUS between day 32 and 47, and mortality was assessed through 77 days.

Results A total of 309 asymptomatic DVTs were detected through CUS. Of these, 133 (4.27%) subjects were in the betrixaban group, and 176 (5.55%) subjects were in the enoxaparin group (relative risk = 0.77, 95% confidence interval [CI] = 0.62–0.97, p = 0.025, number needed to treat = 79). With respect to all-cause mortality due to cardiovascular diseases, non-cardiovascular diseases and unknown causes, the number of the deaths was 5 (1.67%), 4 (1.34%) and 1 (0.33%) in the asymptomatic DVT group and 25 (0.42%), 33 (0.56%) and 11 (0.19%) in the no DVT group, respectively. Subjects with an asymptomatic DVT had an almost threefold increase in the risk of all-cause mortality compared with subjects without DVT (hazard ratio = 2.87, 95% CI = 1.48–5.57, p = 0.001). A positive linear trend was observed between greater thrombus burden and mortality during the follow-up (p = 0.019).

Conclusion Asymptomatic DVT was associated with approximately threefold increased risk of short-term all-cause mortality in patients hospitalized with an acute medical illness within the prior 77 days. A positive linear trend was observed between greater thrombus burden and mortality during the follow-up.