Evaluation of Anti-Xa Apixaban and Rivaroxaban Levels With Respect to Known Doses in Relation to Major Bleeding Events

J Pharm Pract. 2022 Dec;35(6):836-845. doi: 10.1177/08971900211009075. Epub 2021 Apr 12.

Abstract

Background: Although not routinely recommended, anti-Xa level monitoring for apixaban or rivaroxaban may be useful in certain clinical scenarios. There are currently no laboratory standards, therapeutic ranges, or proven correlation between anti-Xa levels and clinical outcomes.

Objective: This study describes the utilization, application, and association of anti-Xa levels with clinical outcomes in patients receiving apixaban or rivaroxaban.

Methods: This retrospective, descriptive study included adult inpatients within the Houston Methodist System on apixaban or rivaroxaban with at least one anti-Xa level ordered subsequent to administered doses. The primary endpoint was major bleeding according to International Society on Thrombosis and Haemostasis criteria. Secondary endpoints included reasons for anti-Xa level ordering, anti-Xa levels at different time intervals post-dose, and thrombotic events. Pre-specified subgroup analyses were performed to further evaluate the primary endpoint.

Results: The study population consisted of 169 patients and 234 anti-Xa levels. Twenty-nine levels were obtained in context of major bleeding. The majority of levels were not drawn as peak levels 2-4 hours post-dose, however remained quantifiable above typical observed levels within this timeframe and well beyond 24 hours post-dose. Patient characteristics with major bleeding included elderly age, acute renal impairment, and low body weight. At least 14 unique reasons for anti-Xa level ordering were identified. Twenty-nine levels were associated with thrombotic events.

Conclusion: Anti-Xa levels may be useful for assessment of current drug concentrations, immediate safety of therapy, and guidance for possible clinical interventions. Dose titration and reversal therapies based on anti-Xa level results in major bleeding warrant further research.

Keywords: anti-Xa apixaban; anti-Xa level; anti-Xa rivaroxaban; bleeding; factor Xa inhibitor.

MeSH terms

  • Adult
  • Aged
  • Factor Xa Inhibitors / adverse effects
  • Hemorrhage / chemically induced
  • Hemorrhage / drug therapy
  • Hemorrhage / epidemiology
  • Heparin, Low-Molecular-Weight
  • Humans
  • Pyridones / adverse effects
  • Retrospective Studies
  • Rivaroxaban* / adverse effects
  • Thrombosis*

Substances

  • Rivaroxaban
  • apixaban
  • Factor Xa Inhibitors
  • Pyridones
  • Heparin, Low-Molecular-Weight