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Severe Bleeding Risk of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Stroke Prevention and Treatment in Patients with Atrial Fibrillation: A Systematic Review and Network Meta-Analysis

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Abstract

Purpose

We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with 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 severe 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

Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1).

Conclusion

Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.

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Availability of Data and Material

All data relevant to the study are included in the article or uploaded as supplementary information.

Code Availability

Not applicable.

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Acknowledgements

This work was supported by grants from the Natural Science Foundation of Fujian Province of China [Grant No. 2018Y0037] and the Fujian Medical Innovation Project [Grant No. 2019-CX-19].

Funding

This work was supported by grants from the Natural Science Foundation of Fujian Province of China [Grant No. 2018Y0037] and the Fujian Medical Innovation Project [Grant No. 2019-CX-19].

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Author notes

  1. Wenlin Xu and Meina Lv contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Fujian Medical University Union Hospital, #29 Xinquan Road, Fuzhou, 350001, China

    Wenlin Xu, Meina Lv, Shuyi Wu, Shaojun Jiang, Zhiwei Zeng, Zongwei Fang, Jiafen Qian, Mingrong Chen, Jiana Chen & Jinhua Zhang

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  1. Wenlin Xu
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Contributions

JZ initiated the study. WX and ML contributed to the conception and design of the study as well as the analysis and interpretation of the data. WX drafted the first version of the manuscript. JZ and WX critically reviewed the manuscript and revised it. WX, ML, and SW contributed to data acquisition and analysis. SJ and JC contributed to the analysis of data and provided critical revisions. ZZ, ZF, JQ, and MC 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.

Corresponding author

Correspondence to Jinhua Zhang.

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Xu, W., Lv, M., Wu, S. et al. Severe Bleeding Risk of Direct Oral Anticoagulants Versus Vitamin K Antagonists for Stroke Prevention and Treatment in Patients with Atrial Fibrillation: A Systematic Review and Network Meta-Analysis. Cardiovasc Drugs Ther 37, 363–377 (2023). https://doi.org/10.1007/s10557-021-07232-9

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