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

• Published in: Thrombosis and haemostasis Vol. 118; no. 12; p. 2046
• Main Authors: Kalayci, Arzu, Gibson, C Michael, Chi, Gerald, Yee, Megan K, Korjian, Serge, Datta, Sudarshana, Nafee, Tarek, Gurin, Mike, Haroian, Noah, Qamar, Iqra, Hull, Russell D, Hernandez, Adrian F, Cohen, Alexander T, Harrington, Robert A, Goldhaber, Samuel Z
• Format: Journal Article
• Language: English
• Published: Germany 01.12.2018
• Subjects: Aged; Aged, 80 and over; Anticoagulants - therapeutic use; Asymptomatic Diseases; Benzamides - therapeutic use; Enoxaparin - therapeutic use; Female; Humans; Male; Proportional Hazards Models; Pyridines - therapeutic use; Risk; Survival Analysis; United States - epidemiology; Venous Thromboembolism - drug therapy; Venous Thromboembolism - epidemiology; Venous Thromboembolism - mortality; Venous Thrombosis - drug therapy; Venous Thrombosis - epidemiology; Venous Thrombosis - mortality; United States
• DOI: 10.1055/s-0038-1675606

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.  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.  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,  = 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,  = 0.001). A positive linear trend was observed between greater thrombus burden and mortality during the follow-up (  = 0.019).  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.