Division of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 18, Bern, 3010, Switzerland.
CTU Bern, University of Bern, Bern, Switzerland.
BMC Nephrol. 2024 Oct 9;25(1):338. doi: 10.1186/s12882-024-03782-w.
Inconsistent study results and contradictory recommendations from health authorities regarding the use of apixaban in patients on hemodialysis have generated considerable uncertainty among clinicians, making investigations of appropriate dosing an unmet need.
We analyzed pre-dialysis apixaban drug levels from a tertiary care dialysis unit, comparing 2.5 mg once versus twice daily dosing. We applied mixed-effects models including dialysis modality, adjusted standard Kt/V, ultrafiltration, and dialyzer characteristics. We included an exploratory analysis of bleeding events and compared the drug levels of our dialysis patients to those from non-CKD reference populations taking the standard dose of 5 mg twice daily.
We analyzed 143 drug levels from 24 patients. Mean (SD) age at first drug level measurement was 64.7 (15.9) years (50 % female), median (IQR) follow-up was 12.5 (5.5 - 21) months. For the apixaban 2.5 mg once and twice daily groups, median (IQR) drug levels were 54.4 (< 40 - 72.1) and 71.3 (48.8 - 104.1) ng/mL respectively (P < 0.001). Levels were below the detection limit in 30 % (with 2.5 mg once daily) and 14 % (with 2.5 mg twice daily) respectively. Only dosing group (twice versus once daily) was independently associated with higher drug levels (P = 0.002). Follow-up did not suggest accumulation. The 95 percentile of drug levels did not exceed those of non-CKD populations taking 5 mg twice daily. Median (IQR) drug levels before a bleeding (8 episodes) were higher than those without a subsequent bleeding: 111.6 (83.1 - 129.3) versus 54.8 (< 40 - 77.1) ng/mL (P < 0.001). Concomitant antiplatelet therapy was used in 86% of those with bleeding events versus 6% without bleeding events (P < 0.001).
Drug monitoring may be a contributory tool to increase patient safety. Despite non-existing target ranges, drug levels on both edges of the spectrum (e.g. below detectability or beyond the 95 percentiles of reference populations) may improve decision-making in highly individualized risk-benefit analyses.
由于在接受血液透析的患者中使用阿哌沙班的研究结果不一致，且卫生当局的建议相互矛盾，这给临床医生带来了相当大的不确定性，使得对适当剂量的研究成为未满足的需求。
我们分析了来自三级护理透析单位的透析前阿哌沙班药物水平，比较了每日 2.5 毫克一次与两次的剂量。我们应用了包括透析方式、调整后的标准 Kt/V、超滤和透析器特征在内的混合效应模型。我们对出血事件进行了探索性分析，并将我们的透析患者的药物水平与接受标准剂量 5 毫克两次每日的非 CKD 参考人群进行了比较。
我们分析了 24 名患者的 143 个药物水平。首次药物水平测量时的平均（SD）年龄为 64.7（15.9）岁（50%为女性），中位（IQR）随访时间为 12.5（5.5-21）个月。对于阿哌沙班每日 2.5 毫克一次和两次的组，中位（IQR）药物水平分别为 54.4（<40-72.1）和 71.3（48.8-104.1）ng/mL（P<0.001）。分别有 30%（每日 2.5 毫克一次）和 14%（每日 2.5 毫克两次）的药物水平低于检测下限。仅剂量组（每日两次与每日一次）与较高的药物水平独立相关（P=0.002）。随访并未提示药物蓄积。药物水平的第 95 百分位数并未超过接受每日两次 5 毫克的非 CKD 人群。（8 例）出血事件前的中位（IQR）药物水平高于无后续出血事件的药物水平：111.6（83.1-129.3）与 54.8（<40-77.1）ng/mL（P<0.001）。有出血事件的患者中有 86%同时使用抗血小板治疗，而无出血事件的患者中只有 6%（P<0.001）。
药物监测可能是提高患者安全性的一种辅助工具。尽管不存在目标范围，但在药物水平的两个极端（例如低于检测下限或超过参考人群的第 95 百分位数）都可能改善高度个体化的风险效益分析中的决策。
