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Thromboprophylaxis with dabigatran etexilate in patients over seventy-five years of age with moderate renal impairment undergoing or knee replacement

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An Erratum to this article was published on 14 February 2012

Abstract

Purpose

Prospective, double-blind studies in orthopaedic patients have been conducted using the direct thrombin inhibitor dabigatran etexilate (hereafter referred to as dabigatran), with two doses investigated and approved for adults (220 mg and 150 mg once daily) to prevent venous thromboembolism (VTE). The European Medicines Agency decided that in major joint orthopaedic surgery, the lower dose should be used in elderly patients (aged over 75 years) and those with reduced renal function (creatinine clearance between 30 and 50 ml/min). Our objective was to understand the efficacy and bleeding data for the lower dose in this subpopulation.

Methods

We extracted and analysed data from the elderly or from moderately renally impaired patients (n 632 of = 5,539) from the orthopaedic clinical development programme of dabigatran.

Results

Dabigatran 150 mg once daily was as effective as the standard European enoxaparin regimen, with numerically fewer major bleeding events. Rates of major VTE were 4.3% vs 6.4% of patients, respectively. Major bleeding events occurred in four (1.3%) vs 11 (3.3%), which shows a trend towards lower bleeding with dabigatran 150 mg [odds ratio (OR) 0.40; 95% confidence interval (CI) 0.13–1.25; p = 0.110]. Mean volume of blood loss was 395 vs 417 ml, and transfused units were 2.4 vs 2.5, respectively. Other safety parameters, including the incidence of wound infections and complications, were similar for 150 mg once daily dabigatran and enoxaparin.

Conclusion

For patients at higher risk of bleeding, dabigatran 150 mg once daily is as effective as enoxaparin following major orthopaedic surgery and is associated with a favourable bleeding rate.

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Acknowledgements

This work was supported by Boehringer Ingelheim. Writing and editorial assistance was provided by Rebecca Gardner, PhD, of PAREXEL, who was contracted by Boehringer Ingelheim for these services. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) and were fully responsible for all content and editorial decisions and were involved at all stages of manuscript development. The authors received no compensation related to the development of the manuscript.

Conflict of interest

OED has been a scientific consultant to AstraZeneca, Bayer/Johnson & Johnson, Boehringer Ingelheim, BMS, GSK, Pfizer and sanofi-aventis. AAK has been a scientific consultant to Boehringer Ingelheim and given presentations on behalf of the company. NR has been a scientific consultant to AstraZeneca, Bayer HealthCare, Boehringer Ingelheim, BMS, GSK, Janssen, Pfizer, and sanofi-aventis. BIE has been a scientific consultant to Astellas, Bayer, Boehringer Ingelheim, BMS and Takeda. HN and AC are employees of Boehringer Ingelheim.

Author information

Authors and Affiliations

  1. Department of Orthopaedics, Elverum Central Hospital, Kirkevn 7, 2418, Elverum, Norway

    Ola E. Dahl

  2. Thrombosis Research Institute, 1 Manresa Road, London, SW3 6LR, UK

    Ola E. Dahl

  3. Orthopaedic University Hospital Mainz, Langenbeckstr. 1, 55131, Mainz, Germany

    Andreas A. Kurth

  4. Department of Anaesthesiology and Intensive Care, Paris Descartes University, Cochin Hospital (AP HP), rue du Faubourg Saint-Jacques, 75014, Paris, France

    Nadia Rosencher

  5. Medical Data Services, Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Strasse 173, 55216, Ingelheim am Rhein, Germany

    Herbert Noack

  6. Department of Medical Affairs, Boehringer Ingelheim GmbH, Binger Strasse 173, 55216, Ingelheim am Rhein, Germany

    Andreas Clemens

  7. Department of Orthopaedic Surgery, University Hospital Sahlgrenska/Östra, Smorslottsgatan 1, 41685, Gothenburg, Sweden

    Bengt I. Eriksson

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  1. Ola E. Dahl
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Corresponding author

Correspondence to Ola E. Dahl.

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Source

The studies were supported by Boehringer Ingelheim GmbH, Germany.

An erratum to this article can be found at http://dx.doi.org/10.1007/s00264-012-1492-y.

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Dahl, O.E., Kurth, A.A., Rosencher, N. et al. Thromboprophylaxis with dabigatran etexilate in patients over seventy-five years of age with moderate renal impairment undergoing or knee replacement. International Orthopaedics (SICOT) 36, 741–748 (2012). https://doi.org/10.1007/s00264-011-1393-5

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