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CC BY 4.0 · TH Open 2022; 06(01): e10-e17
DOI: 10.1055/s-0041-1740492
Original Article

Can a Single Measurement of Apixaban Levels Identify Patients at Risk of Overexposure? A Prospective Cohort Study

Tim A.C. de Vries 
1   Department of Cardiology, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, North Holland, The Netherlands
2   Department of Cardiology, Rijnstate Hospital, Arnhem, Gelderland, The Netherlands
,
Jack Hirsh
3   Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada
4   Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Vinai C. Bhagirath
3   Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada
4   Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Jeffrey S. Ginsberg
3   Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada
4   Department of Medicine, McMaster University, Hamilton, Ontario, Canada
,
Ron Pisters
2   Department of Cardiology, Rijnstate Hospital, Arnhem, Gelderland, The Netherlands
,
Martin E.W. Hemels
2   Department of Cardiology, Rijnstate Hospital, Arnhem, Gelderland, The Netherlands
5   Department of Cardiology, Radboud University Medical Centre, Nijmegen, Gelderland, The Netherlands
,
Joris R. de Groot
1   Department of Cardiology, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, North Holland, The Netherlands
,
John W. Eikelboom
3   Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada
4   Department of Medicine, McMaster University, Hamilton, Ontario, Canada
6   Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
,
Noel C. Chan
3   Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada
4   Department of Medicine, McMaster University, Hamilton, Ontario, Canada
6   Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
› Author Affiliations Funding None of the authors or their institutions have received funding for this project.
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Abstract

Background Patients with atrial fibrillation (AF) are frequently treated with apixaban 2.5-mg twice daily (BID) off-label, presumably to reduce the bleeding risk. However, this approach has the potential to increase the risk of ischemic stroke. If a single measurement could reliably identify patients with high drug levels, the increased stroke risk may be mitigated by confining off-label dose reduction to such patients.

Objectives This study aimed to determine whether a single high apixaban level is predictive of a similarly high level when the test is repeated in 2 months.

Methods In this prospective cohort study of clinic patients receiving apixaban 5-mg BID for AF or venous thromboembolism, peak and trough apixaban levels were measured using the STA-Liquid anti-Xa assay at baseline and 2 months. We calculated the proportions of patients with levels that remained in the upper quintile.

Results Of 100 enrolled patients, 82 came for a second visit, 55 of whom were treated with apixaban 5-mg BID. Seven (63.6%, 95% confidence interval [CI]: 35.4–84.8%) and nine (81.8%, 95% CI: 52.3–94.9%) of 11 patients with a baseline trough and peak level in the upper quintile, respectively, had a subsequent level that remained within this range. Only one (9.1%, 95% CI: 1.6–37.7%) patient had a subsequent level that fell just lower than the median.

Conclusion The trough and peak levels of apixaban in patients who have a high level on a single occasion, usually remain high when the assay is repeated in 2 months. Accordingly, the finding of a high apixaban level in patients deemed to be at high risk of bleeding, allows physicians contemplating off-label use of the 2.5-mg BID dose to limit its use to selected patients who are less likely to be exposed to an increased risk of thrombosis.

Keywords

Biological variation, individual - Biological variation, population - Blood coagulation tests - Drug monitoring - Factor Xa inhibitors - Off-label use

Authors' Contributions

T.A.C. de V., J.H., V.C.B., J.W.E., J.S.G., and N.C.C. have contributed to the concept and design of the study. T.A.C. de V., V.C.B., J.H., J.W.E., and N.C.C. developed the study protocol, designed, and coordinated the study. T.A.C. de V. performed the analyses and prepared the initial draft. T.A.C. de V., J.H., and N.C.C. prepared the first subsequent iterations. All other authors reviewed the ensuing drafts and provided critical comments to produce the final manuscript.


Supplementary Material



Publication History

Received: 19 January 2021

Accepted: 27 October 2021

Article published online:
24 January 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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