Lack of consistency in the relationship between asymptomatic DVT detected by venography and symptomatic VTE in thromboprophylaxis trials

Noel C. Chan; Alexander C. Stehouwer; Jack Hirsh; Jeffrey S. Ginsberg; Ashraf Alazzoni; Michiel Coppens; Gordon H. Guyatt; John W. Eikelboom

doi:10.1160/TH14-12-1006

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2015; 114(05): 1049-1057
DOI: 10.1160/TH14-12-1006

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Lack of consistency in the relationship between asymptomatic DVT detected by venography and symptomatic VTE in thromboprophylaxis trials

Noel C. Chan^*

¹Population Health Research Institute, Hamilton, Ontario, Canada

,

Alexander C. Stehouwer^*

⁵Division of Vascular Medicine, Department of Internal Medicine, University Medical Center Groningen, The Netherlands

,

Jack Hirsh

³Department of Medicine, McMaster University, Hamilton, Ontario, Canada

,

Jeffrey S. Ginsberg

²Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada

³Department of Medicine, McMaster University, Hamilton, Ontario, Canada

,

Ashraf Alazzoni

⁴Department of Cardiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada

,

Michiel Coppens

⁶Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

,

Gordon H. Guyatt

³Department of Medicine, McMaster University, Hamilton, Ontario, Canada

,

John W. Eikelboom

¹Population Health Research Institute, Hamilton, Ontario, Canada

²Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada

³Department of Medicine, McMaster University, Hamilton, Ontario, Canada

› Institutsangaben

Abstract

Summary

Asymptomatic deep-vein thrombosis (DVT) detected by mandatory venography, a surrogate outcome, comprises most of the efficacy outcome events in recent thromboprophylaxis trials. The validity of this surrogate to estimate trade-off between thrombotic and bleeding events in these clinical trials requires a consistent relationship between asymptomatic DVT and symptomatic venous thromboembolism (VTE). In this systematic review of high quality VTE prevention trials, we examined the consistency of the ratios of asymptomatic DVT to symptomatic VTE across a broad range of indications. Studies were identified from citations listed in the chapters on VTE prevention in the antithrombotic guidelines by the American College of Chest Physicians, 2012. A study was eligible if it: 1) was a randomised trial comparing an anticoagulant with standard of care; 2) included at least 500 participants; 3) reported asymptomatic or all DVT rates; and 4) re ported symptomatic VTE rates. Of the 26 eligible trials, 19 trials were conducted in orthopaedic patients, five in general surgery patients and two in general medical patients. The overall median rates (ranges) for asymptomatic DVT and symptomatic VTE were 9.11% (0.75 to 54.87%) and 0.49% (0.00 to 3.10%), respectively. The median ratio was 14.53, with a wide range (2.75 to 103.86). Wide variability in the ratios persisted despite indication- and anticoagulant-specific analyses. In VTE prevention trials of alternative anticoagulants, the wide variability in the ratios of asymptomatic DVT to symptomatic VTE precludes judging the trade-off between thrombotic and bleeding events on the basis of composite outcomes dominated by venographic DVT.

Keywords

Venography - surrogate marker - venous thrombosis - clinical trials - oral anticoagulants - heparins/LMWH

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Referenzen

References
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