Meihandoest Tamana, Studt Jan-Dirk, Mendez Adriana, Alberio Lorenzo, Fontana Pierre, Wuillemin Walter A, Schmidt Adrian, Graf Lukas, Gerber Bernhard, Amstutz Ursula, Bovet Cedric, Sauter Thomas C, Asmis Lars M, Nagler Michael
Department of Epidemiology, Maastricht University, Maastricht, Netherlands.
Department of Clinical Chemistry, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
Front Cardiovasc Med. 2022 Mar 17;9:817826. doi: 10.3389/fcvm.2022.817826. eCollection 2022.
Applying a single anti-Xa assay, calibrated to unfractionated heparin to measure rivaroxaban, apixaban, and edoxaban would simplify laboratory procedures and save healthcare costs.
We hypothesized that a heparin-calibrated anti-Xa assay would accurately measure rivaroxaban, apixaban, and edoxaban drug concentrations and correctly predict clinically relevant drug levels.
This analysis is part of the Simple-Xa study, a prospective multicenter cross-sectional study conducted in clinical practice. Patients treated with rivaroxaban, apixaban, or edoxaban were included. Anti-Xa activity was measured using the Siemens INNOVANCE Heparin assay. Drug concentrations were determined using ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cut-off levels were determined in a derivation dataset (50% of patients) and sensitivities and specificities were calculated in a verification dataset (50% of patients).
Overall, 845 patients were available for analysis. Correlation coefficients (r ) between the heparin-calibrated anti-Xa assay and drug concentrations were 0.97 (95% CI 0.97, 0.98) for rivaroxaban, 0.96 (0.96, 0.97) for apixaban, and 0.96 (0.94, 0.99) for edoxaban. The area under the receiver operating characteristics curve (ROC) was 0.99 for all clinically relevant drug concentrations. In the verification dataset, the sensitivity was 94.2% (95% CI 90.8-96.6) for 30 μg L, 95.8% (92.4-98.0) for 50 μg L, and 98.7% (95.5-99.9) for 100 μg L. Specificities were 86.3% (79.2-91.7), 89.8% (84.5-93.7), and 88.7% (84.2-92.2), respectively.
In a large prospective study in clinical practice, a strong correlation of heparin-calibrated anti-Xa measurements with LC-MS/MS results was observed and clinically relevant drug concentrations were predicted correctly.
应用一种校准至普通肝素的单一抗Xa测定法来检测利伐沙班、阿哌沙班和依度沙班，将简化实验室操作并节省医疗成本。
我们假设肝素校准的抗Xa测定法能准确测量利伐沙班、阿哌沙班和依度沙班的药物浓度，并正确预测临床相关药物水平。
该分析是Simple-Xa研究的一部分，这是一项在临床实践中进行的前瞻性多中心横断面研究。纳入接受利伐沙班、阿哌沙班或依度沙班治疗的患者。使用西门子INNOVANCE肝素测定法测量抗Xa活性。使用超高效液相色谱-串联质谱法（LC-MS/MS）测定药物浓度。在一个推导数据集（50%的患者）中确定临界值水平，并在一个验证数据集（50%的患者）中计算敏感性和特异性。
总体而言，845例患者可用于分析。肝素校准的抗Xa测定法与药物浓度之间的相关系数（r），利伐沙班为0.97（95%CI 0.97, 0.98），阿哌沙班为0.96（0.96, 0.97），依度沙班为0.96（0.94, 0.99）。所有临床相关药物浓度的受试者工作特征曲线（ROC）下面积均为0.99。在验证数据集中，对于30 μg/L，敏感性为94.2%（95%CI 90.8 - 96.6）；对于50 μg/L，敏感性为95.8%（92.4 - 98.0）；对于100 μg/L，敏感性为98.7%（95.5 - 99.9）。特异性分别为86.3%（79.2 - 91.7）、89.8%（84.5 - 93.7）和88.7%（84.2 - 92.2）。
在一项大型临床实践前瞻性研究中，观察到肝素校准的抗Xa测量值与LC-MS/MS结果之间存在强相关性，且能正确预测临床相关药物浓度。
