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Dabigatran Etexilate

A Review of its Use for the Prevention of Venous Thromboembolism after Total Hip or Knee Replacement Surgery

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Abstract

Dabigatran etexilate (Pradaxa®, Pradax™, Prazaxa®) is indicated for the primary prevention of venous thromboembolic (VTE) events in adults who have undergone elective total hip replacement (THR) or total knee replacement (TKR) surgery. This article reviews the clinical efficacy and tolerability of oral dabigatran etexilate in patients undergoing major orthopaedic surgery, as well as summarizing its pharmacological properties and results of a cost-utility analysis. The discussion of clinical trial data focuses on comparative trials with the EU approved dosage regimen of once-daily subcutaneous enoxaparin sodium 40mg.

Dabigatran etexilate is an oral prodrug of the potent, rapidly acting, reversible, competitive inhibitor of thrombin, dabigatran. Dabigatran has predictable and consistent anticoagulant effects and does not require routine coagulation monitoring or dose titration.

In the large, randomized, double-blind, phase III, noninferiority trials, RE-MODEL, RE-NOVATE and RE-NOVATE II, oral dabigatran etexilate, at dosages of 150 and 220 mg once daily, initiated postoperatively was shown to be noninferior to subcutaneous enoxaparin sodium 40 mg once daily (initiated prior to surgery) with regard to the incidence of the composite of total VTE events and all-cause mortality in patients undergoing TKR or THR surgery.

In general, oral dabigatran etexilate was well tolerated in clinical trials of patients undergoing major orthopaedic surgery. There were no significant between-group differences in bleeding complications, including major bleeding, clinically relevant non-major bleeding or minor bleeding between the dabigatran etexilate or enoxaparin sodium groups.

In addition, a cost-utility analysis from the perspective of the UK National Health Service indicated that dabigatran etexilate 220 mg once daily is dominant (i.e. more effective and less costly) to enoxaparin sodium 40 mg once daily in patients undergoing THR or TKR.

Additional head-to-head comparisons would be beneficial to more definitively position dabigatran etexilate relative to other available oral treatment options for VTE prophylaxis, such as rivaroxaban and apixaban. In the meantime, dabigatran etexilate offers a convenient, effective and generally well tolerated treatment option for the prophylaxis of VTE in patients undergoing TKR and THR surgery.

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    Celeste B. Burness & Kate McKeage

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Correspondence to Celeste B. Burness.

Additional information

Various sections of the manuscript reviewed by: W. Dietrich, Institute for Research in Cardiac Anaesthesia, Munich, Germany; S.P. Frostick, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; A. Gallus, Department of Haematology, SA Pathology at Flinders Medical Centre, Flinders University, Adelaide, SA, Australia; T.M. Hyers, CARE Clinical Research, St. Louis, MO, USA; D. Quinlan, Department of Radiology, King’s College Hospital, London, UK; G. Riccioni, Cardiology Unit, San Camillo de Lellis Hospital, Foggia, Italy; J.M. Walenga, Cardiovascular Institute, Loyola University Medical Center, Maywood, IL, USA.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘dabigatran etexilate’ was identified by searching databases (including MEDLINE, EMBASE) for articles published since 1996, bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.

Search strategy: MEDLINE and EMBASE search terms were (‘dabigatran-etexilate’ or ‘dabigatran’) and (‘venous thromboembolism’ or ‘orthopedic’ or ‘orthopaedic’ or ‘hip’ or ‘knee’). Searches were last updated 13 April 2012.

Selection: Studies in patients undergoing major orthopaedic surgery who received dabigatran etexilate. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Dabigatran etexilate, venous thromboembolism, deep vein thrombosis, pulmonary embolism, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

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Burness, C.B., McKeage, K. Dabigatran Etexilate. Drugs 72, 963–986 (2012). https://doi.org/10.2165/11209080-000000000-00000

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