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Meta-Analysis
. 2012 Nov 13:345:e7498.
doi: 10.1136/bmj.e7498.

Efficacy and safety of novel oral anticoagulants for treatment of acute venous thromboembolism: direct and adjusted indirect meta-analysis of randomised controlled trials

Benjamin D Fox  1 , Susan R Kahn, David Langleben, Mark J Eisenberg, Avi Shimony
Affiliations
Meta-Analysis

Efficacy and safety of novel oral anticoagulants for treatment of acute venous thromboembolism: direct and adjusted indirect meta-analysis of randomised controlled trials

Benjamin D Fox et al. BMJ. .

Abstract

Objective: To critically review the effectiveness of the novel oral anticoagulants (rivaroxaban, dabigatran, ximelagatran, and apixaban) in the treatment of acute venous thromboembolism.

Design: Systematic review and random effects meta-analysis. Data were extracted independently by two investigators. An adjusted indirect comparison was performed to compare between novel oral anticoagulants.

Data sources: Medline, Embase, and Cochrane Library (from inception to April 2012). Hand searching of relevant scientific works and contact with experts.

Study selection: Randomised controlled trials of novel oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism. Selected outcomes were recurrent events, major bleeding, and all cause mortality.

Results: Nine studies met our inclusion criteria, involving 16,701 patients evaluated for efficacy and 16,611 for safety. Data were stratified according to different novel oral anticoagulants. For recurrent acute venous thromboembolism, there were no significant differences in events rates between any of the anticoagulants and conventional treatment (rivaroxaban (four studies): relative risk 0.85, 95% confidence interval 0.55 to 1.31; dabigatran (two studies): 1.09, 0.76 to 1.57; ximelagatran (two studies): 1.06, 0.62 to 1.80; and apixaban (one study): 0.98, 0.20 to 4.79). Rivaroxaban reduced the risk of major bleeding compared with conventional treatment (0.57, 0.39 to 0.84), whereas other novel oral anticoagulants did not (0.76 (0.49 to 1.18) for dabigatran; 0.54 (0.28 to 1.03) for ximelagatran; 2.95 (0.12 to 71.82) for apixaban). For all cause mortality there were no significant differences between the novel oral anticoagulants and conventional treatment (0.96 (0.72 to 1.27) for rivaroxaban; 1.00 (0.67 to 1.50) for dabigatran; 0.67 (0.42 to 1.08) for ximelagatran; 6.89 (0.36 to 132.06) for apixaban). The adjusted indirect comparison between rivaroxaban and dabigatran did not show superiority of either drug over the others for major bleeding (0.75, 0.41 to 1.34) or the other endpoints.

Conclusions: Compared with vitamin K antagonists, the novel oral anticoagulants had a similar risk of recurrence of acute venous thromboembolism and all cause mortality, though rivaroxaban was associated with a reduced risk of bleeding.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Flow diagram of search strategy for studies of novel oral anticoagulants for treatment of acute venous thromboembolism
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Fig 2 Relative risk for recurrent venothromboembolism with novel anticoagulants v traditional treatment with vitamin K antagonists
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Fig 3 Relative risk for major bleeding with novel anticoagulants v traditional treatment with vitamin K antagonists
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Fig 4 Relative risk for all cause mortality with novel anticoagulants v traditional treatment with vitamin K antagonists
See this image and copyright information in PMC

References

    1. Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e419-94S. - PMC - PubMed
    1. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G, et al. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e44-88S. - PMC - PubMed
    1. Weitz JI. New oral anticoagulants: a view from the laboratory. Am J Hematol 2012;S1:S133-6. - PubMed
    1. Weitz JI, Eikelboom JW, Samama MM, American College of Chest Physicians. New antithrombotic drugs: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e120-51S. - PMC - PubMed
    1. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions 5.1.0. Cochrane Collaboration, 2011.

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