Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2002; 87(02): 231-237
DOI: 10.1055/s-0037-1612978

Letters to the Editor

Schattauer GmbH

A Dose-ranging Study of the Oral Direct Thrombin Inhibitor, Ximelagatran, and Its Subcutaneous Form, Melagatran, Compared with Dalteparin in the Prophylaxis of Thromboembolism after Hip or Knee Replacement: METHRO I

Bengt I. Eriksson

¹Department of Orthopaedic Surgery, Sahlgrenska University Hospital/Östra, Göteborg

,

Ann-Christin Arfwidsson

²AstraZeneca R&D Mölndal, Mölndal

,

Lars Frison

²AstraZeneca R&D Mölndal, Mölndal

,

Ulf G. Eriksson

²AstraZeneca R&D Mölndal, Mölndal

,

Anders Bylock

²AstraZeneca R&D Mölndal, Mölndal

,

Peter Kälebo

³ Department of Radiology, Sahlgrenska University Hospital/Östra, Göteborg, Sweden

,

Gunnar Fager

²AstraZeneca R&D Mölndal, Mölndal

,

David Gustafsson

²AstraZeneca R&D Mölndal, Mölndal

› Institutsangaben

Summary

The novel, oral direct thrombin inhibitor, ximelagatran (formerly H 376/95), represents an advance in antithrombotic therapy through its oral availability. After oral administration, ximelagatran is converted to its active form, melagatran. Melagatran can also be administered subcutaneously (sc). The results from the first clinical study with ximelagatran are reported. In this randomized, parallel-group, controlled study, 103 patients scheduled for elective total hip or total knee replacement received sc melagatran (1, 2 or 4 mg bid) for 2 days commencing immediately before surgery, followed by oral ximelagatran (6, 12 or 24 mg bid) for 6-9 days. Another 33 patients received dalteparin 5000 IU sc once daily, started the evening before surgery, for 8-11 days. At bilateral venography, deep vein thrombosis was found in 20.5% (16/78) of patients who had received sc melagatran and oral ximelagatran and in 18.5% (5/27) of patients in the dalteparin group. The study did not evaluate a dose-response for efficacy, and no differences between the three dose levels of melagatran and ximelagatran were shown. No pulmonary embolism was diagnosed during treatment. Total bleeding in the sc melagatran plus oral ximelagatran groups showed no dose-response and was similar to that seen in the dalteparin group. The pharmacokinetic properties of melagatran in the surgery patients were consistent with those observed for healthy subjects, and the APTT ratio, which increased non-linearly with plasma melagatran concentration, showed a consistent concentration-effect relationship during the treatment period. Ximelagatran and melagatran were well tolerated. In conclusion, ximelagatran and its active form melagatran appear to be promising agents for the prevention of venous thromboembolism following orthopaedic surgery.

Keywords

Keywords

Deep vein thrombosis - thrombin inhibitors - melagatran - ximelagatran - H 376/95 - oral direct thrombin inhibition

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