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Efficacy and Safety of New Oral Anticoagulants for Extended Treatment of Venous Thromboembolism: Systematic Review and Meta-Analyses of Randomized Controlled Trials

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Abstract

Introduction

Currently available anticoagulants have limitations for long term treatment of venous thromboembolism (VTE).

Objective

A meta-analysis was performed to evaluate the efficacy and safety of new oral anticoagulants (NOACs) for extended treatment of VTE.

Methods

PubMed, Cochrane Library, EMBASE, Web of Science and CINAHL databases were searched from January 01, 2001 through February 28, 2013. Randomized controlled trials (RCTs) comparing NOACs (apixaban, rivaroxaban and dabigatran) with placebo or warfarin for extended treatment of VTE were selected. Primary efficacy outcome was recurrent VTE or VTE related death, and primary safety outcome was major bleeding. We used random-effects models.

Results

Four RCTs included 7,877 participants. NOACs significantly lowered the risk of recurrent VTE or VTE-related death compared to placebo/warfarin (odds ratio [OR] 0.25, 95 % confidence interval [CI] 0.07 to 0.86; number needed to treat [NNT] = 30). All-cause mortality was significantly lower in NOACs group compared to placebo (OR 0.38, 95 % CI 0.18 to 0.80). Risk of major bleeding was not different with NOACs compared to placebo/warfarin (OR 0.88, 95 % CI 0.27 to 2.91). However, NOACs caused significantly higher rate of major or clinically relevant bleeding compared to placebo (OR 2.69, 95 % CI 1.25 to 5.77; number needed to harm [NNH] = 39). All three NOACs (apixaban, rivaroxaban and dabigatran) individually significantly reduced recurrent VTE or VTE-related death compared to placebo. Major or clinically relevant bleeding was higher with dabigatran and rivaroxaban but not with apixaban.

Conclusion

NOACs are effective for the extended treatment of venous thromboembolism and may reduce the risk of all-cause mortality. Dabigatran and rivaroxaban may cause more major or clinically relevant bleeding.

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Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

Partha Sardar, Saurav Chatterjee and Debabrata Mukherjee have no conflicts of interest that might be relevant to the contents of this manuscript.

Authorship

Partha Sardar had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors had access to the data and a role in study design, interpretation and writing of the manuscript.

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Authors and Affiliations

  1. Department of Medicine, New York Medical College-Metropolitan Hospital Center, 1901 First Avenue, New York, NY, USA

    Partha Sardar

  2. Brown University and The Providence VAMC, Providence, RI, USA

    Saurav Chatterjee

  3. Texas Tech University Health Sciences Center, El Paso, TX, USA

    Debabrata Mukherjee

Authors
  1. Partha Sardar
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  2. Saurav Chatterjee
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  3. Debabrata Mukherjee
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Correspondence to Partha Sardar.

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Sardar, P., Chatterjee, S. & Mukherjee, D. Efficacy and Safety of New Oral Anticoagulants for Extended Treatment of Venous Thromboembolism: Systematic Review and Meta-Analyses of Randomized Controlled Trials. Drugs 73, 1171–1182 (2013). https://doi.org/10.1007/s40265-013-0082-7

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  • DOI: https://doi.org/10.1007/s40265-013-0082-7

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