title: Efficacy of delayed thromboprophylaxis with dabigatran: pooled analysis.
abstract: BACKGROUND
  Oral thromboprophylaxis with dabigatran etexilate should be initiated as a half dose 1 to 4h after major orthopaedic surgery. However, a delay in dosing could occur for clinical or logistical reasons. A post hoc analysis was carried out to determine if patients with delayed dosing received adequate anticoagulation.
  
  
  METHODS
  The RE-MODEL™ and RE-NOVATE® trials compared 220 mg and 150 mg dabigatran etexilate with 40 mg enoxaparin. Pooled data for major venous thromboembolism (VTE) and VTE-related mortality (efficacy outcome) and major bleeding events (MBE), MBE/clinically relevant bleeding events, and all bleeding events (safety outcomes) were analysed. Results in patients with dosing delayed more than 4h postsurgery were compared with those of patients without a delay.
  
  
  RESULTS
  Onset of treatment was delayed in 724 (13.3%) of 5425 patients. Efficacy of 220 mg dabigatran etexilate was similar in patients without delayed dosing, patients with a delay and patients with a delay until the day after surgery. Rates of efficacy outcome were higher in patients on 150 mg dabigatran etexilate, but more than 80% of these patients were undertreated based on age or renal clearance status. Some differences in bleeding events were seen among patient groups by treatment arm.
  
  
  CONCLUSIONS
  Dabigatran etexilate thromboprophylaxis should be initiated 1 to 4h postsurgery. Results from our post-hoc analysis indicate that no loss of efficacy appears to occur if initiation of dabigatran etexilate 220 mg needs to be delayed.
authors.affiliation: Department of Orthopaedics, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska University Hospital, SE-43180 Mölndal, Sweden. bengt.eriksson@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
authors.initials: A
authors.lastname: Clemens
authors.forename: Stefan
authors.initials: S
authors.lastname: Hantel
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Kurth
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D000991:Antithrombins / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D000069604:Dabigatran; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017984:Enoxaparin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019637:Orthopedic Procedures / Q000009:adverse effects / Q000379:methods; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage*; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D017984:Enoxaparin; D011725:Pyridines; D000069604:Dabigatran