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Randomized Controlled Trial
. 2021 Feb;10(5):e019459.
doi: 10.1161/JAHA.120.019459. Epub 2021 Feb 15.

Association Between Asymptomatic Proximal Deep Vein Thrombosis and Mortality in Acutely Ill Medical Patients

Gary E Raskob  1 , Alex C Spyropoulos  2 , Alexander T Cohen  3 , Jeffrey I Weitz  4 , Walter Ageno  5 , Yoriko De Sanctis  6 , Wentao Lu  7 , Jianfeng Xu  7 , John Albanese  8 , Chiara Sugarmann  8 , Traci Weber  8 , Concetta Lipardi  8 , Theodore E Spiro  9 , Elliot S Barnathan  8
Affiliations
Randomized Controlled Trial

Association Between Asymptomatic Proximal Deep Vein Thrombosis and Mortality in Acutely Ill Medical Patients

Gary E Raskob et al. J Am Heart Assoc. 2021 Feb.

Abstract

Background Asymptomatic proximal deep vein thrombosis (DVT) is an end point frequently used to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients. Recently, the clinical relevance of asymptomatic DVT has been challenged. Methods and Results The objective of this study was to evaluate the relationship between asymptomatic proximal DVT and all-cause mortality (ACM) using a cohort analysis of a randomized trial for the prevention of venous thromboembolism (VTE) in acutely ill medical patients. Patients who received at least 1 dose of study drug and had an adequate compression ultrasound examination of the legs on either day 10 or day 35 were categorized into 1 of 3 cohorts: no VTE, asymptomatic proximal DVT, or symptomatic DVT. Cox proportional hazards model, with adjustment for significant independent predictors of mortality, were used to compare the incidences of ACM. Of the 7036 patients, 6776 had no VTE, 236 had asymptomatic DVT, and 24 had symptomatic VTE. The incidence of ACM was 4.8% in patients without VTE. Both asymptomatic proximal DVT (mortality, 11.4%; hazard ratio [HR], 2.31; 95% CI, 1.52-3.51; P<0.0001) and symptomatic VTE (mortality, 29.2%; HR, 9.42; 95% CI, 4.18-21.20; P<0.0001) were independently associated with significant increases in ACM. The analysis was post hoc, and ultrasound results were not available for all patients. Adjustment for baseline variables significantly associated with ACM may not fully compensate for differences. Conclusions Asymptomatic proximal DVT is associated with higher ACM than no VTE and remains a relevant end point to evaluate the efficacy of anticoagulant thromboprophylaxis in medical patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00571649.

Keywords: medically ill; mortality; proximal DVT.

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Conflict of interest statement

Dr Raskob received consultant/honoraria fees from Janssen R&D LLC, Bayer, BMS, Daiichi Sankyo, Pfizer, and Medscape; and consultancy fees from Boehringer Ingelheim, Eli Lilly, Portola, Novartis, Anthos, Tetherex, and XaTek. Dr Spyropoulos received consultancy/research funding from Boehringer Ingelheim and consultancy fees from Daiichi Sankyo, Portola, Bayer, ATLAS (Colorado Prevention Center), and Janssen R&D, LLC. Dr Cohen received consultancy/speakers bureau fees from Aspen, Boehringer Ingelheim, and Medscape; consultancy/membership board of directors or advisory committee/speakers bureau fees from Bayer, BMS, Daiichi Sankyo, Pfizer, and Portola; and consultancy fees from AbbVie, ACI Clinical, and Boston Scientific. Dr Weitz received consultant/honoraria fees from Bayer, Boehringer Ingelheim, BMS, Daiichi‐Sankyo, Ionis, Janssen, Merck, Novartis, Pfizer, Servier, and Portola. Dr Ageno received consultant fees from Portola, Daiichi, Sankyo, Aspen, BMS, Pfizer, Boehringer Ingelheim, and Sanofi; and consultant/research funding fees from Bayer and Janssen R&D LLC. Y. De Sanctis is an employee of Bayer US LLC. Dr Lu is an employee with equity ownership of Janssen R&D LLC. Dr Xu is an employee with equity ownership of Janssen R&D LLC. J. Albanese is an employee with equity ownership of Janssen R&D LLC. C. Sugarmann is an employee with equity ownership of Janssen R&D LLC. T. Weber is an employee with equity ownership of Janssen R&D LLC. Dr Lipardi is an employee with equity ownership of Janssen R&D LLC. Dr Spiro was an employee with equity ownership of Bayer US LLC. Dr Barnathan is an employee with equity ownership of Janssen R&D LLC.

Figures

Figure 1
Figure 1. Study disposition.
DVT indicates deep vein thrombosis; mITT 10/mITT 35, modified intent‐to‐treat day 10/day 35 (adequate ultrasound at day 10 or day 35); and VTE, venous thromboembolism.
Figure 2
Figure 2. Time to death from all causes.
DVT indicates deep vein thrombosis; HR, hazard ratio; and VTE, venous thromboembolism.
Figure 3
Figure 3. Survival after detection of asymptomatic proximal DVT vs negative ultrasound: Comparison of survival with and without asymptomatic proximal DVT in (A) MAGELLAN, (B) PREVENT, (C) APEX.
APEX indicates Acute Medically Ill VTE Prevention With Extended Duration Betrixaban study; DVT, deep vein thrombosis; MAGELLAN, Multicenter, Randomized, Parallel Group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Acutely Ill Medical Patients Comparing Rivaroxaban With Enoxaparin study; PREVENT, Prevention of Recurrent Venous Thromboembolism; and VTE, venous thromboembolism. B, Modified from Vaitkus et al 6 with permission. Copyright ©2005 Georg Thieme Verlag KG. C, Modified from Kalayci et al 7 with permission. Copyright ©2018 Georg Thieme Verlag KG.
See this image and copyright information in PMC

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