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Non-major bleeding risk of direct oral anticoagulants versus vitamin K antagonists for stroke prevention with atrial fibrillation: a systematic review and network meta-analysis

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Abstract

Background

Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to non-major bleeding, which may lead to stroke recurrence. We aimed to determine the risk of non-major bleeding using different DOACs to prevent strokes in atrial fibrillation (AF).

Methods

A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting non-major bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated.

Results

Nineteen randomized controlled trials (RCTs) (involving 85,826 patients) were included. For clinically relevant non-major bleeding, the risk for bleeding was lowest for apixaban (SUCRA, 93.9), followed by that for VKAs (SUCRA, 47.7), dabigatran (SUCRA, 40.3), rivaroxaban (SUCRA, 35.9), and edoxaban (SUCRA, 32.2). The minor bleeding safety of DOACs was ranked from highest to lowest as follows: apixaban (SUCRA, 78.1), edoxaban (SUCRA, 69.4), dabigatran (SUCRA, 48.8), and VKAs (SUCRA, 3.7).

Conclusions

Based on current evidence, for stroke prevention in patients with AF, the safest DOAC is apixaban in terms of non-major bleeding. This suggests that apixaban may have a lower risk of non-major bleeding than other anticoagulants and may help provide some clinical reference for choosing a more appropriate drug for the patient.

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The corresponding authors are willing to provide the data related to this manuscript upon reasonable request.

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Acknowledgements

This work was supported by grants from the Science and Technology Innovation Startup Fund of Fujian Maternal and Child Health Hospital (YCXY 23-02).

Funding

This work has been supported by the Science and Technology Innovation Startup Fund of Fujian Maternal and Child Health Hospital (YCXY 23–02).

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JZ initiated the study. FM and WX contributed to the conception and design of the study as well as the analysis and interpretation of the data. FM drafted the first version of the manuscript. JZ and FM critically reviewed the manuscript and revised it. FM, WX, and JC contributed to data acquisition and analysis. WX and JC contributed to the analysis of data and provided critical revisions. FM, WX, and JC contributed to the conception and design, and they provided critical revisions of the paper for crucial intellectual content. All authors read and approved the final manuscript.

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Correspondence to Jinhua Zhang.

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Ma, F., Xu, W., Chen, J. et al. Non-major bleeding risk of direct oral anticoagulants versus vitamin K antagonists for stroke prevention with atrial fibrillation: a systematic review and network meta-analysis. Eur J Clin Pharmacol 79, 1013–1022 (2023). https://doi.org/10.1007/s00228-023-03520-5

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