TH Open (Jan 2022)

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

  • Tim A.C. de Vries,
  • Jack Hirsh,
  • Vinai C. Bhagirath,
  • Jeffrey S. Ginsberg,
  • Ron Pisters,
  • Martin E.W. Hemels,
  • Joris R. de Groot,
  • John W. Eikelboom,
  • Noel C. Chan

DOI
https://doi.org/10.1055/s-0041-1740492
Journal volume & issue
Vol. 06, no. 01
pp. e10 – e17

Abstract

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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.

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