Interpatient Variation in Rivaroxaban and Apixaban Plasma Concentrations in Routine Care

Can J Cardiol. 2017 Aug;33(8):1036-1043. doi: 10.1016/j.cjca.2017.04.008. Epub 2017 Apr 24.

Abstract

Background: Direct-acting oral anticoagulants (DOACs) are widely prescribed for stroke prevention in patients with atrial fibrillation (AF). An important advantage of DOACs is that routine monitoring of an anticoagulation response is not necessary. Nevertheless, because of their mechanism of action, a DOAC anticoagulation effect can be inferred based on the observed plasma concentration. However, there is a paucity of data relating to observed interpatient variation in DOAC plasma concentrations in the postmarket clinical setting.

Methods: We determined rivaroxaban and apixaban plasma concentrations in patients with AF during routine clinic visits.

Results: Among 243 patients (rivaroxaban, n = 94; apixaban, n = 149) enrolled in this study, a 60- and 50-fold interpatient variation in plasma concentration was observed for rivaroxaban and apixaban, respectively. Approximately 12% of patients receiving rivaroxaban and 13% of patients receiving apixaban exceeded the 95th percentile for predicted maximum plasma concentration observed in clinical trials.

Conclusions: In this routine-care setting, rivaroxaban and apixaban plasma concentrations tended to be more variable than those observed in clinical trials. Identification of additional clinical and molecular determinants that more fully predict patients at risk for excessively high or low DOAC concentrations may enable a more precise DOAC dosing regimen for the individual patient.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Atrial Fibrillation / blood
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Dose-Response Relationship, Drug
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / pharmacokinetics
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Pyrazoles / administration & dosage
  • Pyrazoles / pharmacokinetics*
  • Pyridones / administration & dosage
  • Pyridones / pharmacokinetics*
  • Rivaroxaban / administration & dosage
  • Rivaroxaban / pharmacokinetics*
  • Stroke / etiology
  • Stroke / prevention & control*
  • Time Factors

Substances

  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • apixaban
  • Rivaroxaban

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