Reda Sara, Rudde Eva, Müller Jens, Hamedani Nasim Shahidi, Oldenburg Johannes, Pötzsch Bernd, Rühl Heiko
Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
Life (Basel). 2022 May 8;12(5):705. doi: 10.3390/life12050705.
Direct oral anticoagulants (DOACs) apixaban and rivaroxaban are broadly used in the management of venous thromboembolism (VTE). Although not routinely required, measurement of their plasma concentration is advised for an increasing number of indications. Due to the lack of therapeutic ranges, current guidelines recommend reporting DOAC plasma levels together with expected levels from previous pivotal studies. The aim of this study was to assess DOAC level variation in a large VTE patient population. Drug concentrations determined by measurement of the anti-Xa-activity using drug-specific calibrators in citrated plasma samples from patients on rivaroxaban (n = 1471) or apixaban (n = 725) were analyzed. Observed 5th-95th percentile ranges of apixaban peak/trough levels (63-299/13-114 ng/mL for 5 mg, 37-161/7-68 ng/mL for 2.5 mg twice daily) were similar to previously reported mass-spectrometry-based reference data, and 10th-90th percentile ranges of rivaroxaban peak/trough levels (98-367/8-55 ng/mL for 20 mg, 51-211/5-27 ng/mL for 10 mg once daily) were even narrower. Age and drug levels correlated weakly (r ≤ 0.330). Drug levels measured repeatedly in subgroups of patients showed a strong correlation (r ≥ 0.773). In conclusion, anti-Xa-activity-based measurement of apixaban and rivaroxaban yields reliable results. However, the paucity of levels off-range underlines the need for evidence-based thresholds to better assist clinical decision making.
直接口服抗凝剂（DOACs）阿哌沙班和利伐沙班广泛用于静脉血栓栓塞症（VTE）的管理。尽管并非常规必需，但对于越来越多的适应证，建议测定其血浆浓度。由于缺乏治疗范围，当前指南建议报告DOAC血浆水平以及先前关键研究中的预期水平。本研究的目的是评估大量VTE患者群体中DOAC水平的变化。分析了在接受利伐沙班（n = 1471）或阿哌沙班（n = 725）治疗的患者的枸橼酸盐血浆样本中，使用药物特异性校准物通过测定抗Xa活性所确定的药物浓度。观察到的阿哌沙班峰/谷水平的第5至95百分位数范围（5 mg时为63 - 299/13 - 114 ng/mL，每日两次2.5 mg时为37 - 161/7 - 68 ng/mL）与先前报道的基于质谱的参考数据相似，利伐沙班峰/谷水平的第10至90百分位数范围（20 mg时为98 - 367/8 - 55 ng/mL，每日一次10 mg时为51 - 211/5 - 27 ng/mL）甚至更窄。年龄与药物水平的相关性较弱（r≤0.330）。在患者亚组中重复测量的药物水平显示出很强的相关性（r≥0.773）。总之，基于抗Xa活性测定阿哌沙班和利伐沙班可产生可靠结果。然而，超出范围的水平较少，这凸显了需要基于证据的阈值以更好地辅助临床决策的必要性。
