title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Statistical analyses of efficacy and safety in subgroups of the METHRO III intention-to-treat population.
  
  
  METHODS
  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/ximelagatran 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.
authors.affiliation: Thrombosis Research Institute, London, UK.
authors.forename: Ola E
authors.initials: OE
authors.lastname: Dahl
authors.forename: Bengt I
authors.initials: BI
authors.lastname: Eriksson
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Agnelli
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Cohen
authors.forename: Patrick
authors.initials: P
authors.lastname: Mouret
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosencher
authors.forename: Seva
authors.initials: S
authors.lastname: Panfilov
authors.forename: Anders
authors.initials: A
authors.lastname: Bylock
authors.forename: Magnus
authors.initials: M
authors.lastname: Andersson