Gulilat Markus, Tang Anthony, Gryn Steven E, Leong-Sit Peter, Skanes Allan C, Alfonsi Jeffrey E, Dresser George K, Henderson Sara L, Rose Rhiannon V, Lizotte Daniel J, Teft Wendy A, Schwarz Ute I, Tirona Rommel G, Kim Richard B
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.
Division of Cardiology, Department of Medicine, London Health Sciences Centre, Western University, London, Ontario, Canada.
Can J Cardiol. 2017 Aug;33(8):1036-1043. doi: 10.1016/j.cjca.2017.04.008. Epub 2017 Apr 24.
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.
We determined rivaroxaban and apixaban plasma concentrations in patients with AF during routine clinic visits.
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.
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.
直接口服抗凝剂（DOACs）被广泛用于预防心房颤动（AF）患者的中风。DOACs的一个重要优点是无需常规监测抗凝反应。然而，由于其作用机制，可以根据观察到的血浆浓度推断DOAC的抗凝效果。然而，在上市后临床环境中，关于DOAC血浆浓度患者间差异的数据很少。
我们在常规门诊就诊时测定了AF患者的利伐沙班和阿哌沙班血浆浓度。
在本研究纳入的243例患者（利伐沙班，n = 94；阿哌沙班，n = 149）中，利伐沙班和阿哌沙班的血浆浓度患者间差异分别为60倍和50倍。接受利伐沙班治疗的患者中约12%以及接受阿哌沙班治疗的患者中约13%超过了临床试验中观察到的预测最大血浆浓度的第95百分位数。
在这种常规护理环境中，利伐沙班和阿哌沙班的血浆浓度往往比临床试验中观察到的更具变异性。确定更多能够更全面预测DOAC浓度过高或过低风险患者的临床和分子决定因素，可能有助于为个体患者制定更精确的DOAC给药方案。
