Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Br J Clin Pharmacol. 2024 Dec;90(12):3221-3231. doi: 10.1111/bcp.16211. Epub 2024 Aug 15.
To investigate plasma apixaban concentrations and thrombin generation assay (TGA) parameters across different apixaban doses in atrial fibrillation patients who had dose-reduction criteria for apixaban.
This observational study included 374 patients (mean age 75.6 ± 7.7 years, 54.8% female) with dose-reduction criteria for apixaban. The patients were divided into 3 groups: (i) on-label standard dose (5 mg twice daily, n = 166); (ii) on-label reduced dose (2.5 mg twice daily, n = 55); and (iii) off-label underdose (2.5 mg twice daily, n = 153). Apixaban concentrations determined via the anti-Xa assay and TGA parameters were compared at trough levels.
The off-label underdose group exhibited significantly lower apixaban trough concentrations than the on-label reduced-dose and standard-dose groups (56.7 ± 42.9 vs. 83.7 ± 70.4 vs. 129.9 ± 101.8 ng/mL, all P < .001). Less than 70% of all patients fell within the expected range of apixaban concentrations. Proportions exceeding the upper limit of the expected range were significantly lower in the off-label underdose group (1.3%) than in the on-label reduced-dose (9.1%, P = .005) and standard-dose (12.7%, P < .001) groups. The TGA parameters showed the on-label standard-dose group displaying the lowest thrombogenic profiles. Lower creatinine clearance was the most significant predictor of higher apixaban concentrations.
Off-label underdosed apixaban resulted in lower apixaban concentrations than both on-label standard and reduced-dose regimens. A considerable proportion of the patients exhibited apixaban concentrations outside the expected range, suggesting the potential benefits of plasma concentration monitoring. Further studies are needed to compare dosages directly, investigate the impact of plasma apixaban concentration monitoring and validate the current dose-reduction criteria.
研究存在依伐沙班剂量调整标准的房颤患者中，依伐沙班不同剂量下的血浆依伐沙班浓度和凝血酶生成试验（TGA）参数。
本观察性研究纳入了 374 例（平均年龄 75.6±7.7 岁，54.8%为女性）存在依伐沙班剂量调整标准的患者。患者分为 3 组：（i）标准剂量组（5 mg，每日 2 次，n=166）；（ii）标准剂量降低组（2.5 mg，每日 2 次，n=55）；（iii）低剂量组（2.5 mg，每日 2 次，n=153）。通过抗-Xa 测定法测定依伐沙班浓度，并比较达峰水平时的 TGA 参数。
低剂量组的依伐沙班达峰浓度明显低于标准剂量降低组和标准剂量组（56.7±42.9 比 83.7±70.4 比 129.9±101.8 ng/ml，均 P<0.001）。不到 70%的患者的依伐沙班浓度处于预期范围内。低剂量组的依伐沙班浓度超过预期范围上限的比例明显低于标准剂量降低组（1.3%比 9.1%，P=0.005）和标准剂量组（12.7%，P<0.001）。TGA 参数显示标准剂量组的血栓形成特征最低。较低的肌酐清除率是依伐沙班浓度较高的最显著预测因子。
依伐沙班低剂量给药导致的依伐沙班浓度低于标准剂量和标准剂量降低剂量方案。相当一部分患者的依伐沙班浓度超出预期范围，提示进行血浆浓度监测可能带来益处。需要进一步的研究来直接比较剂量，探讨血浆依伐沙班浓度监测的影响，并验证当前的剂量调整标准。
