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Efficacy and safety of rivaroxaban versus apixaban for venous thromboembolism: A systematic review and meta-analysis of observational studies

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Abstract

Background

Direct-acting oral anticoagulants (DOACs) including rivaroxaban and apixaban are preferred over vitamin K antagonists for the treatment of venous thromboembolism (VTE). We conducted a systematic review and a meta-analysis to compare the efficacy and safety of rivaroxaban versus apixaban in the treatment of VTE.

Methods

We conducted an electronic search for studies that directly compared treatment with rivaroxaban and apixaban in adult patients with VTE. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated and pooled using a fixed-effect model unless significant heterogeneity was present (I2 > 40%), then random-effects model was used. The primary efficacy and safety outcomes were recurrent VTE (rVTE) and major bleeding events, respectively.

Results

Nine observational studies were included in our meta-analysis, assessing 24,156 patients for apixaban and 38,847 for rivaroxaban. Pooling of data for our primary efficacy outcome showed a trend towards lower risk of rVTE with apixaban compared to rivaroxaban (RR 0.77, 95% CI 0.57–1.04, I2 = 53%). Analysis of our primary safety outcome showed a significantly lower risk of major bleeding with apixaban compared to rivaroxaban (RR 0.68, 95% CI 0.61–0.76, I2 = 0%). Apixaban was associated with significantly decreased risk of net clinical harm, clinically relevant non major bleeding (CRNMB) and any bleeding, compared to rivaroxaban (RR 0.75, 95% CI 0.61–0.92, I2 = 50%; RR 0.58, 95% CI 0.50–0.67, I2 = 7%; RR 0.64, 95% CI 0.59–0.70, I2 = 0%, respectively).

Conclusions

Apixaban is associated with a significantly lower risk of major bleeding compared to rivaroxaban for treatment of VTE. Given the limitations of the existing evidence, further interventional studies comparing the two drugs are needed.

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Data availability

The data that support the findings of this study are available from the corresponding author, [DF], upon reasonable request.

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Funding

This research received no specific grant or financial support from any external institution.

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Authors and Affiliations

  1. Internal Medicine Department A, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel

    Danielle Fredman, Rotem McNeil, Ofir Eldar, Anat Gafter-Gvili & Tomer Avni

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel

    Danielle Fredman, Rotem McNeil, Ofir Eldar, Avi Leader, Anat Gafter-Gvili & Tomer Avni

  3. Institute of Haematology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel

    Avi Leader & Anat Gafter-Gvili

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  1. Danielle Fredman
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Contributions

DF: Database search, data extraction and risk of bias assessment of included studies, data analysis, interpretation and writing. RM: Database search, data extraction and risk of bias assessment of included studies, data analysis and interpretation. OE: Database search, data extraction and risk of bias assessment of included studies, data analysis and interpretation. AL: Data analysis, interpretation, and writing. AG-G: Study design, data analysis interpretation and writing. TA: Study design, data analysis, interpretation and writing and overall supervision.

Corresponding author

Correspondence to Danielle Fredman.

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Competing interests

Avi Leader declares honoraria for lectures and scientific advisory boards for Bayer, Pfizer, Sanofi, Leo-pharma. Anat Gafter-Gvili declares honoraria for lectures and advisory board from Pfizer, Bayer, Sanofi, Medison. All remaining authors have declared no conflicts of interest.

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Fredman, D., McNeil, R., Eldar, O. et al. Efficacy and safety of rivaroxaban versus apixaban for venous thromboembolism: A systematic review and meta-analysis of observational studies. J Thromb Thrombolysis 57, 453–465 (2024). https://doi.org/10.1007/s11239-023-02926-3

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