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Comparative Study
. 2016 Aug 3;11(8):e0160064.
doi: 10.1371/journal.pone.0160064. eCollection 2016.

Comparison of the Non-VKA Oral Anticoagulants Apixaban, Dabigatran, and Rivaroxaban in the Extended Treatment and Prevention of Venous Thromboembolism: Systematic Review and Network Meta-Analysis

A T Cohen  1 , M Hamilton  2 , A Bird  3 , S A Mitchell  4 , S Li  2 , R Horblyuk  5 , S Batson  4
Affiliations
Comparative Study

Comparison of the Non-VKA Oral Anticoagulants Apixaban, Dabigatran, and Rivaroxaban in the Extended Treatment and Prevention of Venous Thromboembolism: Systematic Review and Network Meta-Analysis

A T Cohen et al. PLoS One. .

Erratum in

Abstract

Background: Historically, warfarin or aspirin have been the recommended therapeutic options for the extended treatment (>3 months) of VTE. Data from Phase III randomised controlled trials (RCTs) are now available for non-VKA oral anticoagulants (NOACs) in this indication. The current systematic review and network meta-analysis (NMA) were conducted to compare the efficacy and safety of anticoagulants for the extended treatment of VTE.

Methods: Electronic databases (accessed July 2014 and updated April 2016) were systematically searched to identify RCTs evaluating apixaban, aspirin, dabigatran, edoxaban, rivaroxaban, and warfarin for the extended treatment of VTE. Eligible studies included adults with an objectively confirmed deep vein thrombosis, pulmonary embolism or both. A fixed-effect Bayesian NMA was conducted, and results were presented as relative risks (RRs). Sensitivity analyses examining (i) the dataset employed according to the time frame for outcome assessment (ii) the model used for the NMA were conducted.

Results: Eleven Phase III RCTs (examining apixaban, aspirin, dabigatran, rivaroxaban, warfarin and placebo) were included. The risk of the composite efficacy outcome (VTE and VTE-related death) was statistically significantly lower with the NOACs and warfarin INR 2.0-3.0 compared with aspirin, with no significant differences between the NOACs. Treatment with apixaban (RR 0.23, 95% CrI 0.10, 0.55) or dabigatran (RR 0.55, 95% Crl 0.43, 0.71) was associated with a statistically significantly reduced risk of 'major or clinically relevant non-major bleed' compared with warfarin INR 2.0-3.0. Apixaban also showed a significantly reduced risk compared with dabigatran (RR 0.42, 95% Crl 0.18, 0.97) and rivaroxaban (RR 0.23, 95% Crl 0.09, 0.59). Sensitivity analyses indicate that results were dependent on the dataset, but not on the type of NMA model employed.

Conclusions: Results from the NMA indicate that NOACs are an effective treatment for prevention of VTE or VTE-related death) in the extended treatment setting. However, bleeding risk differs between potential treatments, with apixaban reporting the most favourable profile compared with other NOACs, warfarin INR 2.0-3.0, and aspirin.

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Conflict of interest statement

Competing Interests: The authors of this manuscript have the following interests: This study was funded by Bristol-Myers Squibb and Pfizer. MH and SL are employed by Bristol-Myers Squibb, RH by Pfizer Ltd, and SB and SAM by DRG Abacus. AB was employed by Pfizer Ltd when the study was conducted. ATC was a paid consultant to Bristol-Myers Squibb and Pfizer in connection with the development of this manuscript. SAM and SB are employees of DRG Abacus and were paid consultants to Bristol-Myers Squibb and Pfizer Ltd in connection with conducting this study and with the development of this manuscript. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Fig 1
Fig 1. Systematic review flow diagram.
The flow diagram indicates inclusion and exclusion of publications at each stage of the systematic review process. †An updated search was conducted in April 2016. No additional eligible publications were identified.
Fig 2
Fig 2. Network of evidence for the primary outcome of ‘VTE and VTE-related death’.
† The WODIT PE study was only included in the sensitivity analysis based on outcome data from the intended follow-up period (sensitivity analysis 2).
See this image and copyright information in PMC

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