title: A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial.
abstract: BACKGROUND
  Dabigatran etexilate is an oral direct thrombin inhibitor undergoing evaluation for the prevention of venous thromboembolism (VTE) following orthopedic surgery.
  
  
  METHODS
  In a multicenter, parallel-group, double-blind study, 1973 patients undergoing total hip or knee replacement were randomized to 6-10 days of oral dabigatran etexilate (50, 150 mg twice daily, 300 mg once daily, 225 mg twice daily), starting 1-4 h after surgery, or subcutaneous enoxaparin (40 mg once daily) starting 12 h prior to surgery. The primary efficacy outcome was the incidence of VTE (detected by bilateral venography or symptomatic events) during treatment.
  
  
  RESULTS
  Of the 1949 treated patients, 1464 (75%) patients were evaluable for the efficacy analysis. VTE occurred in 28.5%, 17.4%, 16.6%, 13.1% and 24% of patients assigned to dabigatran etexilate 50, 150 mg twice daily, 300 mg once daily, 225 mg twice daily and enoxaparin, respectively. A significant dose-dependent decrease in VTE occurred with increasing doses of dabigatran etexilate (P < 0.0001). Compared with enoxaparin, VTE was significantly lower in patients receiving 150 mg twice daily [odds ratio (OR) 0.65, P = 0.04], 300 mg once daily (OR 0.61, P = 0.02) and 225 mg twice daily (OR 0.47, P = 0.0007). Compared with enoxaparin, major bleeding was significantly lower with 50 mg twice daily (0.3% vs. 2.0%, P = 0.047) but elevated with higher doses, nearly reaching statistical significance with the 300 mg once-daily dose (4.7%, P = 0.051).
  
  
  CONCLUSIONS
  Oral administration of dabigatran etexilate, commenced early in the postoperative period, was effective and safe across a range of doses. Further optimization of the efficacy/safety balance will be addressed in future studies.
authors.affiliation: Sahlgrenska University Hospital/Ostra, Göteborg, Sweden. b.eriksson@orthop.gu.se
authors.forename: B I
authors.initials: BI
authors.lastname: Eriksson
authors.forename: O E
authors.initials: OE
authors.lastname: Dahl
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
authors.forename: R
authors.initials: R
authors.lastname: Hettiarachchi
authors.forename: N
authors.initials: N
authors.lastname: Rosencher
authors.forename: M-L
authors.initials: ML
authors.lastname: Bravo
authors.forename: L
authors.initials: L
authors.lastname: Ahnfelt
authors.forename: F
authors.initials: F
authors.lastname: Piovella
authors.forename: J
authors.initials: J
authors.lastname: Stangier
authors.forename: P
authors.initials: P
authors.lastname: Kälebo
authors.forename: P
authors.initials: P
authors.lastname: Reilly
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000494:pharmacology*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D000069604:Dabigatran; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017984:Enoxaparin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011183:Postoperative Complications; D011184:Postoperative Period; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D012044:Regression Analysis; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013923:Thromboembolism / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D017984:Enoxaparin; D011725:Pyridines; D013917:Thrombin; D000069604:Dabigatran