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A Benefit-Risk Assessment of Dabigatran in the Prevention of Venous Thromboembolism in Orthopaedic Surgery

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Abstract

Dabigatran etexilate is a novel orally administered anticoagulant that exerts its action through reversible direct thrombin inhibition. This anticoagulant has been approved for prophylaxis against venous thromboembolism (VTE) after hip or knee arthroplasty, and in a few countries also for atrial fibrillation. This article reviews the efficacy and safety of dabigatran for the prophylaxis of VTE-indication compared with data on the most common current regimen with low-molecular-weight heparin (LMWH), specifically enoxaparin.

Alternative prophylactic agents are also discussed. The results regarding efficacy and safety are very similar for dabigatran and LMWH. Bleeding and gastrointestinal reactions are the most frequently reported adverse events with a comparable incidence on LMWH and are probably the result of surgery and anaesthaesia. No adverse event that is specific for dabigatran has been observed in these studies, although dyspepsia has been reported as significantly more frequent than warfarin in long-term studies on other indications. The fact that dabigatran has no antidote has so far not been a problem in patients undergoing orthopaedic surgery. The use of the lower dose of dabigatran (150 mg) appears beneficial to reduce the risk of bleeding in patients over 75 years of age and in those with moderate renal impairment to avoid drug accumulation. The convenience of oral administration is an advantage for dabigatran over LMWH, particularly for extended prophylaxis up to 1 month after surgery. In conclusion, the benefit-risk profile of dabigatran is favourable for use as prophylaxis against VTE after major orthopaedic surgery with its convenient oral administration without need for laboratory monitoring and a low risk of bleeding or other adverse events.

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Acknowledgements

Dr Schulman reports receiving consulting fees from Boehringer Ingelheim and Astra-Zeneca for membership of steering committees and from GlaxoSmith-Kline and Sanofi-Aventis for membership in drug safety monitoring boards; honoraria from LEO Pharma, Sanofi-Aventis and Boehringer Ingelheim for lectures and from Bayer Healthcare and Boehringer Ingelheim for participation in advisory boards; and an unrestricted educational grant to his university from Bayer HealthCare. Dr Majeed has no conflicts of interest. No financial support was obtained for the writing of this manuscript.

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  1. Department of Medicine, McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada

    Sam Schulman

  2. Department of Hematology, Karolinska University Hospital and Institute, Stockholm, Sweden

    Sam Schulman & Ammar Majeed

  3. Department of Medicine, Mälar Hospital, Eskilstuna, Sweden

    Ammar Majeed

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Schulman, S., Majeed, A. A Benefit-Risk Assessment of Dabigatran in the Prevention of Venous Thromboembolism in Orthopaedic Surgery. Drug-Safety 34, 449–463 (2011). https://doi.org/10.2165/11587290-000000000-00000

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