Regular Article Dabigatran versus enoxaparin for prevention of venous thromboembolism after hip or knee arthroplasty: A pooled analysis of three trials R.J. Friedman a, ⁎, O.E. Dahl b , N. Rosencher c , J.A. Caprini d , A.A. Kurth e , C.W. Francis f , A. Clemens g , S. Hantel h , J.M. Schnee i , B.I. Eriksson j for the RE-MOBILIZE, RE-MODEL, RE-NOVATE Steering Committees a Medical University of South Carolina and Charleston Orthopedic Associates, Charleston, South Carolina, USA b Thrombosis Research Institute, London, United Kingdom and Elverum Central Hospital, Norway c Paris Descartes University and Cochin Hospital (AP HP), Paris, France d NorthShore University HealthSystem, Evanston IL and Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA e University Medical Centre, Mainz, Germany f University of Rochester Medical Center, Rochester, New York, USA g Boehringer Ingelheim GmbH, Ingelheim, Germany h Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany i Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut, USA j University Hospital Sahlgrenska/Östra, Gothenburg, Sweden abstract article info Article history: Received 4 February 2010 Received in revised form 8 March 2010 Accepted 27 March 2010 Available online 15 May 2010 Keywords: Dabigatran Total knee arthroplasty Total hip arthroplasty Prophylaxis Venous thromboembolism Background: Three randomized, double-blind trials compared dabigatran, an oral direct thrombin inhibitor, with enoxaparin for the primary prevention of venous thromboembolism (VTE) in patients undergoing elective total hip and knee arthroplasty. Objectives and Methods: We conducted a pre-specified pooled analysis of these trials. 8,210 patients were randomized, of whom 8,135 were treated (evaluable for safety) with dabigatran 220 mg or 150 mg once- daily, or subcutaneous enoxaparin (40 mg once-daily or 30 mg twice-daily). Efficacy analyses were based on the modified intention-to-treat population of 6,200 patients with an evaluable outcome. The common risk difference (RD) of treatment effect between each dabigatran dose and enoxaparin was estimated using fixed-effects models, and statistical heterogeneity was estimated using the I 2 statistic. Results: The composite outcome of major VTE (proximal deep vein thrombosis and/or pulmonary embolism) and VTE-related mortality occurred in 3.3% of the enoxaparin group versus 3.0% of the dabigatran 220 mg group (RD vs. enoxaparin -0.2%, 95% CI -1.3% to 0.9%, I 2 = 37%) and 3.8% of the 150 mg group (RD vs. enoxaparin 0.5%, -0.6% to 1.6%, I 2 = 0%). Major bleeding occurred in 1.4% of the enoxaparin group versus 1.4% of the dabigatran 220 mg group (RD vs. enoxaparin -0.2%, -0.8% to 0.5%, I 2 =40%) and 1.1% of the 150 mg group (RD vs. enoxaparin -0.4%, -1.0% to 0.2%, I 2 = 0%). Conclusions: Oral dabigatran was as effective as subcutaneous enoxaparin in reducing the risk of major VTE and VTE-related mortality after hip or knee arthroplasty and has a similar bleeding profile. © 2010 Elsevier Ltd. All rights reserved. Current standard practice for anticoagulant prophylaxis to prevent venous thromboembolism (VTE) after total hip or knee arthroplasty includes subcutaneous low-molecular weight heparin (LMWH) [1]. However, parenteral administration may limit optimal patient care, particularly when outpatient dosing is required after early hospital discharge. Dabigatran etexilate (hereafter termed dabigatran) is an oral, reversible direct thrombin inhibitor (DTI), with predictable and repro- ducible pharmacodynamic effects and pharmacokinetic characteristics that permit once-daily dosing [2]. To date, more than 30,000 patients have been studied in clinical trials [3–9], and more than 7,000 individuals are enrolled in ongoing trials. Three major prospective, randomized, double-blind non-inferiority trials have compared the efficacy and safety of dabigatran (150 mg or 220 mg once-daily) starting postoperatively, with subcutaneous enoxaparin, in patients undergoing hip (RE-NOVATE) [5] or knee arthroplasty (RE-MOBILIZE [6] and RE-MODEL [7]). The trials were of similar design with identical efficacy and safety endpoints assessed by independent adjudication committees using the same criteria. The primary efficacy endpoint in each trial was a composite of total VTE (either venographic or symptomatic deep-vein thrombosis [DVT] or pulmonary embolism [PE]) and all-cause mortality during treatment. Thrombosis Research 126 (2010) 175–182 ⁎ Corresponding author. Charleston Orthopedic Associates, 1012 Physicians Drive, Charleston, SC 29414, USA. Tel.: +1 843 769 2000; fax: +1 843 769 2260. E-mail address: rjfriedman@mybones.com (R.J. Friedman). 0049-3848/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2010.03.021 Contents lists available at ScienceDirect Thrombosis Research journal homepage: www.elsevier.com/locate/thromres