Elsevier

The Journal of Arthroplasty

Volume 32, Issue 2, February 2017, Pages 645-652
The Journal of Arthroplasty

Review
Safety and Efficacy of New Anticoagulants for the Prevention of Venous Thromboembolism After Hip and Knee Arthroplasty: A Meta-Analysis

https://doi.org/10.1016/j.arth.2016.09.033Get rights and content

Abstract

Background

Venous thromboembolism (VTE) is a common and potentially fatal complication of arthroplasty.

Methods

We reviewed randomized trials to determine which anticoagulant has the best safety and efficacy in hip and knee arthroplasty patients. We searched PubMed, MEDLINE, and EMBASE through January 2016.

Results

Compared to enoxaparin (most commonly dosed 40 mg once daily), the relative risk (RR) of VTE was lowest for edoxaban 30 mg once daily (0.49; 95% confidence interval [CI], 0.32-0.75), fondaparinux 2.5 mg once daily (0.53; 95% CI, 0.45-0.63), and rivaroxaban 10 mg once daily (0.55; 95% CI, 0.46-0.66), and highest for dabigatran 150 mg once daily (1.19; 95% CI; 0.98-1.44). The RR of major/clinically relevant bleeding was lowest for apixaban 2.5 mg twice daily (0.84; 95% CI; 0.70-0.99) and highest for rivaroxaban (1.27; 95% CI, 1.01-1.59) and fondaparinux (1.64; 95% CI, 0.24-11.35). Fondaparinux was the only agent that was more effective than enoxaparin 30 mg twice daily (VTE RR = 0.58; 95% CI, 0.43-0.76).

Conclusion

With the possible exception of apixaban, newer anticoagulants that lower the risk of postoperative VTE increase bleeding.

Section snippets

Data Sources and Searches

We searched PubMed, MEDLINE (through PubMed), and EMBASE through January 2016 using the following keywords: (apixaban OR dabigatran OR rivaroxaban OR fondaparinux OR edoxaban) AND (hip OR knee) AND arthroplasty. Additionally, references of included studies were reviewed as potential candidate trials. No betrixaban or darexaban trials met our inclusion criteria.

Study Selection

Inclusion criteria were as follows: double-blinded, randomized, controlled trials that enrolled adult patients within 48 hours of

Results

Initial searches located 435 trials. After applying inclusion/exclusion criteria (Fig. 1), 4 apixaban trials, 4 dabigatran trials, 4 fondaparinux trials, 4 rivaroxaban trials, and 2 edoxaban trials were included. All 18 trials were sponsored by the manufacturers. The control in every trial was enoxaparin (given subcutaneously). Although the enoxaparin regimen varied across trials, its consistent use enabled us to compare the safety and efficacy of each new anticoagulant against enoxaparin. With

Discussion

As compared to subcutaneous enoxaparin, 4 newer anticoagulants reduced the rate of VTE after arthroplasty (Fig. 2). Their RR (95% CI) were as follows: apixaban, 0.71 (0.52-0.96); rivaroxaban, 0.55 (0.46-0.66); fondaparinux, 0.53 (0.45-0.63); and edoxaban, 0.49 (0.32-0.75). Apixaban also protected against major/clinically relevant bleeding: RR (95% CI) of 0.84 (0.70-0.99). In contrast, rivaroxaban increased major/clinically relevant bleeds (RR = 1.27; 95% CI, 1.01-1.59). The effect of

Acknowledgments

Funding for this research was provided by the NIH grant HL R01 HL097036, UL1 RR024992, and TL1 RR024995.

References (42)

  • A.K. Kakkar et al.

    Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial

    Lancet

    (2008)
  • T. Fuji et al.

    Safety and efficacy of edoxaban, an oral factor Xa inhibitor, versus enoxaparin for thromboprophylaxis after total knee arthroplasty: the STARS E-3 trial

    Thromb Res

    (2014)
  • J.A. Caprini et al.

    Effective risk stratification of surgical and nonsurgical patients for venous thromboembolic disease

    Semin Hematol

    (2001)
  • V. Kulshrestha et al.

    DVT prophylaxis after TKA: routine anticoagulation vs risk screening approach - a randomized study

    J Arthroplasty

    (2013)
  • D.M. Witt et al.

    Chapter 26. Venous thromboembolism

  • S.M. Kurtz et al.

    Future young patient demand for primary and revision joint replacement: national projections from 2010 to 2030

    Clin Orthop Relat Res

    (2009)
  • Points to consider on clinical investigation of medicinal products for prophylaxis of intra and post-operative venous thromboembolic risk

    (2007)
  • M.R. Lassen et al.

    Apixaban or enoxaparin for thromboprophylaxis after knee replacement

    N Engl J Med

    (2009)
  • M.R. Lassen et al.

    Apixaban versus enoxaparin for thromboprophylaxis after hip replacement

    N Engl J Med

    (2010)
  • RE-MOBILIZE Writing Committee et al.

    Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery

    J Arthroplasty

    (2009)
  • B.I. Eriksson et al.

    Oral dabigatran versus enoxaparin for thromboprophylaxis after primary total hip arthroplasty (RE-NOVATE II*). A randomised, double-blind, non-inferiority trial

    Thromb Haemost

    (2011)
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    A poster of the abstract and preliminary results were presented at the 2012 American College of Clinical Pharmacy in Hollywood, Florida.

    No author associated with this paper has disclosed any potential or pertinent conflicts which may be perceived to have impending conflict with this work. For full disclosure statements refer to http://dx.doi.org/10.1016/j.arth.2016.09.033.

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