Oral Factor Xa inhibitors, such as apixaban and rivaroxaban, have revolutionized anticoagulation therapy, providing effective stroke prevention and treatment for thromboembolic disorders. However, the widespread adoption of these agents has led to significant challenges in managing bleeding complications, particularly before the approval of specific reversal agents. This Research Topic aims to delve into the history, current practices, and future directions of reversing oral Factor Xa inhibitors, with a special focus on the rampant off-label use of 4-Factor Prothrombin Complex Concentrates (PCCs) like KCentra in the United States and other countries.

The scope of this Research Topic includes:
- A historical review of the initial clinical landscape before the approval of specific reversal agents.
- Examination of the off-label use of 4-Factor PCCs, highlighting the clinical decisions, guidelines, and their evolution over time.
- Comparative analysis of prospective and retrospective studies on PCC treatment for Xa inhibitor bleeding patients, discussing the level of evidence and limitations of these studies.
- Evaluation of recent clinical trials, including the ANNEXa-I trial which compares andexanet alfa to usual medical care, providing insights into its implications for clinical practice.
- Projections on the future landscape, considering the impending generic status of rivaroxaban and apixaban and the anticipated impact on usage rates and bleeding complications.
- Discussion of healthcare system errors and lessons learned, drawing analogies to past mistakes to better understand how we arrived at current practices.

We invite the submission of various types of articles including:
- Original Research articles presenting new data or novel insights.
- Review articles summarizing the current knowledge and identifying gaps.
- Case Reports illustrating unique clinical scenarios.
- Opinion articles and Commentaries discussing the controversies and future pathways.
-Meta-analyses and Systematic Reviews synthesizing existing research.

The overall aim of this Research Topic is to provide a comprehensive understanding of the challenges and advancements in reversing oral Factor Xa inhibitors, fostering informed clinical decision-making, and driving future research in this critical area of cardiovascular medicine.

*Topic Editor Charles Edward Mahan is currently employed by Astra-Zeneca however this project was initiated prior to his employment. Topic Editor Mark Goldin received research grants from Janssen Scientific Affairs. Topic Editor Alex Spyropoulos received research grants from Janssen and Astra Zeneca and is a consultant for Janssen, Astra Zeneca, Bayer, Bristol Meyer Squibb, Sanofi, and Daichi Sankyo.
Topic Editor Jessica Grandoni reports no competing interests related to this Research Topic.

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Reversal of Oral Factor Xa Inhibitors: Historical Insights, Current Practices, and Future Directions