Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.
PLoS One. 2024 Jul 31;19(7):e0308022. doi: 10.1371/journal.pone.0308022. eCollection 2024.
Catheter ablation in patients with atrial fibrillation is associated with a transient increase in thromboembolic risk and adequate anticoagulation is highly important. When patients are anticoagulated with apixaban, monitoring of plasma concentrations of the drug is not routinely performed. This study aimed to assess the influence of clinical patient characteristics, concomitant drug treatment and self-reported adherence on apixaban concentrations, and to describe the intra- and inter-individual variability in apixaban concentrations in this group of patients. Method Apixaban concentrations from 141 patients were measured in plasma one week before ablation and two, six and ten weeks after ablation, employing ultra-high performance liquid chromatography coupled with tandem mass spectrometry. In samples not obtained at trough, apixaban concentrations were adjusted to trough levels. Self-reported adherence was registered by means of the 8-item Morisky Medication Adherence Scale before and after ablation.
There were statistically significant, positive correlations between apixaban concentrations and increased age, female sex, lower glomerular filtration rate, higher CHA2DS2-VASc score, use of cytochrome P450 3A4 and/or p-glycoprotein inhibitors, and use of amiodarone. Self-reported adherence was generally high. The mean intra-individual and inter-individual coefficients of variation were 29% and 49%, respectively.
In patients undergoing catheter ablation for atrial fibrillation, age, sex, renal function, interacting drugs and cerebrovascular risk profile were all associated with altered plasma apixaban concentration. In this group of patients with a generally high self-reported adherence, intra-individual variability was modest, but the inter-individual variability was substantial, and similar to those previously reported in other patient apixaban-treated populations. If a therapeutic concentration range is established, there might be a need for a more flexible approach to apixaban dosing, guided by therapeutic drug monitoring.
在房颤患者中进行导管消融术与短暂的血栓栓塞风险增加有关，因此高度重视充分抗凝治疗至关重要。当患者接受阿哌沙班抗凝治疗时，通常不会监测药物的血浆浓度。本研究旨在评估临床患者特征、合并药物治疗和自我报告的用药依从性对阿哌沙班浓度的影响，并描述该组患者中阿哌沙班浓度的个体内和个体间变异性。方法：采用超高效液相色谱-串联质谱法，检测 141 例患者消融前一周、消融后两周、六周和十周的血浆中阿哌沙班浓度。在未达到谷浓度时的样本中，将阿哌沙班浓度调整至谷浓度。在消融前后，通过 8 项 Morisky 用药依从性量表来记录自我报告的用药依从性。结果：阿哌沙班浓度与年龄增加、女性、肾小球滤过率降低、CHA2DS2-VASc 评分较高、使用细胞色素 P450 3A4 和/或 p-糖蛋白抑制剂以及使用胺碘酮呈正相关。自我报告的用药依从性普遍较高。个体内和个体间变异系数的平均值分别为 29%和 49%。结论：在接受导管消融术治疗房颤的患者中，年龄、性别、肾功能、相互作用的药物以及脑血管风险谱都与改变的阿哌沙班血浆浓度相关。在该组自我报告的用药依从性普遍较高的患者中，个体内变异较小，但个体间变异较大，与之前在其他接受阿哌沙班治疗的患者人群中报告的结果相似。如果建立了治疗浓度范围，可能需要更灵活的方法来指导治疗药物监测下的阿哌沙班剂量调整。
