Clinical Drug Investigation

, Volume 25, Issue 1, pp 65–77

Postoperative Melagatran/ Ximelagatran for the Prevention of Venous Thromboembolism following Major Elective Orthopaedic Surgery

Effects of Timing of First Dose and Risk Factors for Thromboembolism and Bleeding Complications on Efficacy and Safety
  • Ola E. Dahl
  • Bengt I. Eriksson
  • Giancarlo Agnelli
  • Alexander T. Cohen
  • Patrick Mouret
  • Nadia Rosencher
  • Seva Panfilov
  • Anders Bylock
  • Magnus Andersson
Original Research Article

DOI: 10.2165/00044011-200525010-00006

Cite this article as:
Dahl, O.E., Eriksson, B.I., Agnelli, G. et al. Clin. Drug Investig. (2005) 25: 65. doi:10.2165/00044011-200525010-00006

Abstract

Objectives: To examine the influence of timing of postoperative initiation of subcutaneous melagatran followed by oral ximelagatran, and of risk factors for venous thromboembolism (VTE; including deep vein thrombosis [DVT] and pulmonary embolism [PE]) and bleeding complications, on the efficacy and safety of this regimen, compared with preoperative enoxaparin sodium, following total hip replacement (THR) or total knee replacement (TKR) surgery.

Design: Statistical analyses of efficacy and safety in subgroups of the METHRO III intention-to-treat population.

Main outcome measures: Main efficacy outcome measures were major VTE (proximal DVT, PE or VTE-related death) and total VTE (distal or proximal DVT, fatal or non-fatal PE). The main safety outcome measures were blood transfusion, severe bleeding events, blood loss, bleeding-related adverse events and need for reoperation.

Results: In the combined THR and TKR population, melagatran initiated 4–<8 hours postoperatively was non-inferior to enoxaparin sodium with respect to the risks of total VTE (absolute risk reduction [ARR] 0; 95% confidence interval [CI] ∼-4.4, 4.4) and major VTE (ARR −0.63; 95% CI −2.94, 1.67). The rate of major VTE was unaffected by the different risk factors. In the combined THR and TKR population, blood transfusion requirements were lower with melagatran/ximela-gatran than enoxaparin sodium (odds ratio 0.83; 95% CI 0.71, 0.96; p = 0.016).

Conclusions: Melagatran/ximelagatran initiated 4–<8 hours postoperatively provided a comparable level of protection against total and major VTE to preoperative enoxaparin sodium. Major VTE rates and safety were consistent across different patient subgroups. Subcutaneous melagatran followed by fixed-dose oral ximelagatran offers an alternative to the standard European low molecular-weight heparin regimen in a wide range of patients.

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Ola E. Dahl
    • 1
  • Bengt I. Eriksson
    • 2
  • Giancarlo Agnelli
    • 3
  • Alexander T. Cohen
    • 4
  • Patrick Mouret
    • 5
  • Nadia Rosencher
    • 6
  • Seva Panfilov
    • 7
  • Anders Bylock
    • 7
  • Magnus Andersson
    • 7
  1. 1.Thrombosis Research Institute, Emmanuel Kaye BuildingLondonUK
  2. 2.Sahlgrenska University Hospital/ÖstraGöteborgSweden
  3. 3.University of PerugiaPerugiaItaly
  4. 4.Guy’s, King’s and St Thomas’ School of MedicineLondonUK
  5. 5.Frankfurt-Höchst ClinicFrankfurtGermany
  6. 6.Paris M 5 University and Cochin HospitalParisFrance
  7. 7.AstraZeneca R&D MölndalMölndalSweden

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