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Thromb Haemost 2003; 89(02): 288-296
DOI: 10.1055/s-0037-1613445
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Direct thrombin inhibitor melagatran followed by oral ximelagatran in comparison with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement

The METHRO III study
Bengt I. Eriksson
1   Department of Orthopaedics, Sahlgrenska University Hospital/östra, Göteborg, Sweden
,
Giancarlo Agnelli
2   Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy
,
Alexander T. Cohen
3   Department of Academic Surgery, Guy’s, King’s, Thomas’ School of Medicine, London, UK
,
Ola E. Dahl
4   Department of Orthopaedics, Research Forum, Ullevaal University Hospital, Oslo, Norway
,
Patrick Mouret
5   Department of Orthopaedics Frankfurt-Höchst Clinic, Frankfurt, Germany
,
Nadia Rosencher
6   Department of Orthopaedics, Cochin Hospital, Paris, France
,
Christina Eskilson
7   AstraZeneca Research and Development, Mölndal, Sweden
,
Ingela Nylander
7   AstraZeneca Research and Development, Mölndal, Sweden
,
Lars Frison
7   AstraZeneca Research and Development, Mölndal, Sweden
,
Mats ögren
7   AstraZeneca Research and Development, Mölndal, Sweden
,
on behalf of the METHRO III Study Group* (* see Appendix for METHRO III study participants) › Author Affiliations Financial support: This study was supported by a research grant from AstraZeneca, Mölndal, Sweden. AstraZeneca sponsored METHRO III and provided all study medication and materials.
Further Information

Publication History

Received 28 August 2002

Accepted after revision 27 November 2002

Publication Date:
07 December 2017 (online)

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Summary

We evaluated whether a postoperative regimen with melagatran followed by oral ximelagatran, two new direct thrombin inhibitors, was an optimal regimen for thromboprophylaxis in major orthopaedic surgery. In a double-blind study, 2788 patients undergoing total hip or knee replacement were randomly assigned to receive for 8 to 11 days either 3 mg of subcutaneous melagatran started 4-12 h postoperatively, followed by 24 mg of oral ximelagatran twice-daily or 40 mg of subcutaneous enoxaparin once-daily, started 12 h preoperatively. Ximelagatran was to be initiated within the first two postoperative days. The primary efficacy endpoint was venous thromboembolism (deep-vein thrombosis detected by mandatory venography, pulmonary embolism or unexplained death). The main safety endpoint was bleeding. Venous thromboembolism occurred in 355/1146 (31.0%) and 306/1122 (27.3%) patients in the ximelagatran and enoxaparin group, respectively, a difference in risk of 3.7% in favour of enoxaparin (p = 0.053). Bleeding was comparable between the two groups.

Keywords

Venous thromboembolism - joint replacement surgery - thrombin inhibitors - ximelagatran/melagatran - enoxaparin
 

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