title: Dabigatran is effective with a favourable safety profile in normal and overweight patients undergoing major orthopaedic surgery: a pooled analysis.
abstract: BACKGROUND
  Three pivotal phase 3 trials have demonstrated that oral dabigatran etexilate showed similar safety and efficacy to enoxaparin 40 mg once daily (qd) for venous thromboembolism (VTE) prevention in patients undergoing total knee or hip replacement. Obesity is an established independent risk factor for VTE.
  
  
  METHODS
  A post-hoc pooled analysis of the three trials was performed to evaluate the safety and efficacy of dabigatran 220 mg qd versus enoxaparin 40 mg qd in patients with a normal body mass index (BMI) of >20-25 kg/m(2), pre-obese patients (BMI >25-30 kg/m(2)) and obese patients (BMI >30 kg/m(2)). The primary efficacy endpoint was major VTE and VTE-related mortality; safety endpoints included major, clinically relevant, or any bleeding events.
  
  
  RESULTS
  The mean BMIs for patients in the dabigatran and enoxaparin arms from all three trials, separately, were between 27.5 and 29.9 kg/m(2). Of the participants, 1417 (24.9%) had a normal BMI, 2373 (41.7%) were pre-obese and 1826 (32.1%) obese. In patients with normal BMI, the rates of the primary efficacy endpoint were significantly lower in the dabigatran than in the enoxaparin group (2.1% versus 4.3%; OR 0.48; 95% CI 0.24-0.97, P=0.037). No significant difference between dabigatran and enoxaparin in the primary efficacy endpoint was observed in the other subgroups. Bleeding rates were also similar between treatments for BMI subgroups.
  
  
  CONCLUSIONS
  Dabigatran is an effective thromboprophylactic therapy for normal, pre-obese and obese patients, and outcomes in patients with a BMI >25 kg/m(2) do not differ from the overall population.
authors: Department of Ortopaedics, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska University Hospital, SE-43180 Mölndal, Sweden. b.eriksson@orthop.gu.se
authors: Bengt I
authors: BI
authors: Eriksson
authors: Ola E
authors: OE
authors: Dahl
authors: Martin
authors: M
authors: Feuring
authors: Andreas
authors: A
authors: Clemens
authors: Herbert
authors: H
authors: Noack
authors: Stefan
authors: S
authors: Hantel
authors: Richard J
authors: RJ
authors: Friedman
authors: Michael
authors: M
authors: Huo
mesh_terms: D000368:Aged; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects / Q000379:methods*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects / Q000379:methods*; D001562:Benzimidazoles / Q000009:adverse effects* / Q000627:therapeutic use*; D015992:Body Mass Index; D017326:Clinical Trials, Phase III as Topic; D000069604:Dabigatran; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D011183:Postoperative Complications / Q000517:prevention & control; D012307:Risk Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000188:drug therapy / Q000517:prevention & control*; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D001562:Benzimidazoles; D015091:beta-Alanine; D000069604:Dabigatran