Markus Gulilat1, Anthony Tang2, Steven E Gryn3, Peter Leong-Sit2, Allan C Skanes2, Jeffrey E Alfonsi3, George K Dresser3, Sara L Henderson3, Rhiannon V Rose4, Daniel J Lizotte4, Wendy A Teft3, Ute I Schwarz1, Rommel G Tirona1, Richard B Kim5. 1. Division of Clinical Pharmacology, Department of Medicine, London Health Sciences Centre, Western University, London, Ontario, Canada; Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. 2. Division of Cardiology, Department of Medicine, London Health Sciences Centre, Western University, London, Ontario, Canada. 3. Division of Clinical Pharmacology, Department of Medicine, London Health Sciences Centre, Western University, London, Ontario, Canada. 4. Departments of Computer Science, Epidemiology & Biostatistics, Western University, London, Ontario, Canada. 5. Division of Clinical Pharmacology, Department of Medicine, London Health Sciences Centre, Western University, London, Ontario, Canada; Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. Electronic address: richard.kim@lhsc.on.ca.
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.
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.
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