Authors: Eriksson B.I.¹; Agnelli G.²; Cohen A.T.³; Dahl O.E.⁴; Lassen M.R.⁵; Mouret P.⁶; Rosencher N.⁷; Kälebo P.¹; Panfilov S.⁸; Eskilson C.⁸; Andersson M.⁸

Source: Journal of Thrombosis and Haemostasis, Volume 1, Number 12, December 2003 , pp. 2490-2496(7)

Publisher: Wiley-Blackwell

Abstract:

Summary.

Background: Ximelagatran and its subcutaneous (s.c.) form melagatran are novel direct thrombin inhibitors for the prevention and treatment of thromboembolic disease. Methods: In a double-blind study, 2835 consecutive patients undergoing total hip or knee replacement were randomized to either melagatran/ximelagatran or enoxaparin. Melagatran 2 mg was started immediately before surgery; 3 mg was then administered postoperatively, followed by 24 mg of oral ximelagatran b.i.d. beginning the next day. Enoxaparin 40 mg, administered subcutaneously o.d., was started 12 h before surgery. Both treatments were continued for 8–11 days. The main efficacy outcome measures were major venous thromboembolism (VTE); [proximal deep vein thrombosis (DVT), non-fatal and/or fatal pulmonary embolism (PE), death where PE could not be ruled out], and total VTE (proximal and distal DVT; PE; death from all causes). DVT was detected by mandatory bilateral ascending venography at the end of the treatment period or earlier if clinically suspected. The main safety outcome was bleeding. Results: The rates of major and total VTE were significantly lower in the melagatran/ximelagatran group compared with the enoxaparin group (2.3% vs. 6.3%, P = 0.0000018; and 20.3% vs. 26.6%, P < 0.0004, respectively). Fatal bleeding, critical site bleeding and bleeding requiring reoperation did not differ between the two groups. ‘Excessive bleeding as judged by the investigator’ was more frequent with melagatran/ximelagatran than with enoxaparin. Conclusions: In patients undergoing total hip or knee replacement, preoperatively initiated s.c. melagatran followed by oral ximelagatran was significantly more effective in preventing VTE than preoperatively initiated s.c. enoxaparin.

Keywords: deep vein thrombosis; oral direct thrombin inhibition; ximelagatran

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1538-7836.2003.00494.x

Affiliations: 1: Department of Orthopedics and Department of Radiology, Sahlgrenska University Hospital/Östra, Göteborg, Sweden; 2: Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy; 3: Academic Department of Surgery, Guy's, King's and St Thomas' School of Medicine, London, UK; 4: Department of Orthopedics, Section for Joint Implants and Medical Science, Buskerud Central Hospital, Norway; 5: Department of Orthopedics, University Hospital of Copenhagen, Hillerød, Denmark; 6: Department of Orthopedics, Frankfurt-Höchst Clinic, Frankfurt, Germany; 7: Department of Anesthesiology, Cochin University Hospital, Paris, France; and 8: AstraZeneca R&D, Mölndal, Sweden

Publication date: 2003-12-01

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