title: Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial.
abstract: BACKGROUND
  After hip replacement surgery, prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism. Our aim was to assess the oral, direct thrombin inhibitor dabigatran etexilate for such prophylaxis.
  
  
  METHODS
  In this double-blind study, we randomised 3494 patients undergoing total hip replacement to treatment for 28-35 days with dabigatran etexilate 220 mg (n=1157) or 150 mg (1174) once daily, starting with a half-dose 1-4 h after surgery, or subcutaneous enoxaparin 40 mg once daily (1162), starting the evening before surgery. The primary efficacy outcome was the composite of total venous thromboembolism (venographic or symptomatic) and death from all causes during treatment. On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo, the non-inferiority margin for the difference in rates of thromboembolism was defined as 7.7%. Efficacy analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00168818.
  
  
  RESULTS
  Median treatment duration was 33 days. 880 patients in the dabigatran etexilate 220 mg group, 874 in the dabigatran etexilate 150 mg group, and 897 in the enoxaparin group were available for the primary efficacy outcome analysis; the main reasons for exclusion in all three groups were the lack of adequate venographic data. The primary efficacy outcome occurred in 60 (6.7%) of 897 individuals in the enoxaparin group versus 53 (6.0%) of 880 patients in the dabigatran etexilate 220 mg group (absolute difference -0.7%, 95% CI -2.9 to 1.6%) and 75 (8.6%) of 874 people in the 150 mg group (1.9%, -0.6 to 4.4%). Both doses were thus non-inferior to enoxaparin. There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin (p=0.44 for 220 mg, p=0.60 for 150 mg). The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups.
  
  
  CONCLUSIONS
  Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery, with a similar safety profile.
authors.affiliation: Department of Orthopaedic Surgery, Sahlgrenska University Hospital/Ostra, Gothenburg, Sweden. b.eriksson@orthop.gu.se
authors.forename: Bengt I
authors.initials: BI
authors.lastname: Eriksson
authors.forename: Ola E
authors.initials: OE
authors.lastname: Dahl
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosencher
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Kurth
authors.forename: C Niek
authors.initials: CN
authors.lastname: van Dijk
authors.forename: Simon P
authors.initials: SP
authors.lastname: Frostick
authors.forename: Martin H
authors.initials: MH
authors.lastname: Prins
authors.forename: Rohan
authors.initials: R
authors.lastname: Hettiarachchi
authors.forename: Stefan
authors.initials: S
authors.lastname: Hantel
authors.forename: Janet
authors.initials: J
authors.lastname: Schnee
authors.forename: Harry R
authors.initials: HR
authors.lastname: Büller
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000069604:Dabigatran; D004311:Double-Blind Method; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D013923:Thromboembolism / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D017984:Enoxaparin; D011725:Pyridines; D000069604:Dabigatran