Adverse events of direct factor Xa inhibitors: a disproportionality analysis of the FAERS database

ABSTRACT

Objectives

Direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, commonly used direct oral anticoagulant (DOAC), are widely used to prevent and treat stroke and venous thromboembolic events in patients with atrial fibrillation (AF). This study aimed to assess and compare reports of adverse events associated with rivaroxaban, apixaban, and edoxaban, including hemorrhagic and non-hemorrhagic events.

Methods

Reporting odds ratio (ROR), proportional reporting ratio (PRR), Medications and Health Care Products Regulatory Agency (MHRA), and the information component (IC) were used to perform a risk assessment of adverse event reports in the FDA Adverse Event Reporting System (FAERS) database for the years 2018–2022.

Results

Combined with disproportionality analysis in different backgrounds, the salient risks of the three-factor Xa inhibitors varied. Rivaroxaban had the most significant risk of hemorrhage, apixaban had a higher incidence and risk of death, cardiac and cerebral adverse events, and edoxaban showed a more prominent risk in the kidneys and urinary system.

Conclusion

Hemorrhage is a common risk with factor Xa inhibitors, with rivaroxaban being the most significant. Apixaban and edoxaban also showed significant association with non-hemorrhagic adverse events, and increased attention to non-hemorrhagic adverse events is needed in clinical use.

KEYWORDS:

• Rivaroxaban
• apixaban
• edoxaban
• FAERS
• adverse events
• signal generation

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Y Qian: methodology, literature search, data extraction, and analysis, and wrote the manuscript; X Zhao: data analysis, reviewed and revised the manuscript; D Liu: literature search; J Liu: literature search; Z Yue: literature search; W Liu: study conception and revised the manuscript. All authors gave final approval and agreed to be responsible for all aspects of the work.

Availability of data and material

The datasets analyzed during the current study are available in the public domain: https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html

Ethical approval

This article does not contain any studies with human participants performed by any of the authors. This study is based on anonymous data that can be downloaded from a publicly available source. Therefore, no ethical approval was required.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2024.2368815

Additional information

Funding

This paper was not funded.