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A systematic review of contemporary trials of anticoagulants in orthopaedic thromboprophylaxis: suggestions for a radical reappraisal

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Abstract

In the last decade, major advances in venous thromboembolism (VTE) prophylaxis in orthopaedic surgery have included the development of new anticoagulants that are poised to replace low molecular weight heparins (LMWHs) and improvements in operative and perioperative care that have likely led to a decline in the rates of symptomatic VTE and mortality independent of anticoagulant use. A systematic review of the literature was performed to identify phase III randomized controlled trials of VTE prevention that compared new anticoagulants (fondaparinux, rivaroxaban, dabigatran, apixaban) with LMWH (enoxaparin) in major elective orthopaedic surgery. Our aims were to obtain best estimates of the rates of patient important events (symptomatic VTE, mortality, and bleeding) in contemporary trials of VTE prevention, and to consider the implications of these contemporary rates for clinical practice and future research. Fourteen studies, which enrolled 40,285 patients, were included in the analyses. The combined median rates (ranges) for all five anticoagulants for symptomatic VTE and mortality to the end of follow-up were 0.99 % (0.15–2.58 %) and 0.26 % (0–0.92 %) respectively, whereas the median rate (range) of clinically important bleeding was 3.44 % (2.25–7.74 %). In contemporary trials of anticoagulants, the rates of symptomatic VTE and mortality are low, but the rates of clinically important post-operative bleeding remain relatively high. Based on these results, we propose that approaches that minimize bleeding without substantially reducing efficacy merit investigation, particularly if improvement in surgical and perioperative care have also resulted in falling baseline patient important VTE rates independent of anticoagulant use.

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Acknowledgment

NCC received an educational grant from the Haematology Society of Australia and New Zealand.

Conflicts of interest

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf. JWE has received consulting fees and/or honoraria from Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol-Myer-Squibb, Daiichi-Sankyo, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Sanofi-Aventis, and has received grants and/or in-kind support from Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol-Myer-Squibb, Glaxo-Smith-Kline, Pfizer, Janssen, Sanofi-Aventis. All other authors declare no competing financial interest.

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Authors and Affiliations

  1. Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada

    Noel C. Chan, Mandy N. Lauw, Jeffrey S. Ginsberg, John W. Eikelboom & Jack Hirsh

  2. Population Health Research Institute, 237 Barton St E, Hamilton, ON, L7l 2X2, Canada

    Noel C. Chan, Mandy N. Lauw & John W. Eikelboom

  3. Department of Medicine, McMaster University, Hamilton, Canada

    Deborah Siegal, Jeffrey S. Ginsberg, John W. Eikelboom, Gordon H. Guyatt & Jack Hirsh

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  1. Noel C. Chan
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  2. Deborah Siegal
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Correspondence to Noel C. Chan.

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Chan, N.C., Siegal, D., Lauw, M.N. et al. A systematic review of contemporary trials of anticoagulants in orthopaedic thromboprophylaxis: suggestions for a radical reappraisal. J Thromb Thrombolysis 40, 231–239 (2015). https://doi.org/10.1007/s11239-014-1153-7

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