血液透析中的阿哌沙班剂量--药物浓度监测能否缓解争议?

IF 2.2 4区 医学 Q2 UROLOGY & NEPHROLOGY BMC Nephrology Pub Date : 2024-10-09 DOI:10.1186/s12882-024-03782-w
Simeon Schietzel, Andreas Limacher, Matthias B Moor, Cecilia Czerlau, Uyen Huynh-Do, Bruno Vogt, Fabienne Aregger, Dominik E Uehlinger
{"title":"血液透析中的阿哌沙班剂量--药物浓度监测能否缓解争议?","authors":"Simeon Schietzel, Andreas Limacher, Matthias B Moor, Cecilia Czerlau, Uyen Huynh-Do, Bruno Vogt, Fabienne Aregger, Dominik E Uehlinger","doi":"10.1186/s12882-024-03782-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sup>th</sup> 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).</p><p><strong>Conclusions: </strong>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<sup>th</sup> percentiles of reference populations) may improve decision-making in highly individualized risk-benefit analyses.</p>","PeriodicalId":9089,"journal":{"name":"BMC Nephrology","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465812/pdf/","citationCount":"0","resultStr":"{\"title\":\"Apixaban dosing in hemodialysis - can drug level monitoring mitigate controversies?\",\"authors\":\"Simeon Schietzel, Andreas Limacher, Matthias B Moor, Cecilia Czerlau, Uyen Huynh-Do, Bruno Vogt, Fabienne Aregger, Dominik E Uehlinger\",\"doi\":\"10.1186/s12882-024-03782-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sup>th</sup> 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).</p><p><strong>Conclusions: </strong>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<sup>th</sup> percentiles of reference populations) may improve decision-making in highly individualized risk-benefit analyses.</p>\",\"PeriodicalId\":9089,\"journal\":{\"name\":\"BMC Nephrology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2024-10-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465812/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Nephrology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12882-024-03782-w\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12882-024-03782-w","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:关于血液透析患者使用阿哌沙班的研究结果不一致,卫生部门的建议也相互矛盾,这给临床医生带来了很大的不确定性,因此对适当剂量的研究成为一项尚未满足的需求:我们分析了一家三级医疗透析单位透析前的阿哌沙班药物水平,比较了 2.5 毫克每日一次和每日两次的剂量。我们采用了混合效应模型,包括透析方式、调整后的标准 Kt/V、超滤和透析器特征。我们对出血事件进行了探索性分析,并将透析患者的药物水平与每日两次服用 5 毫克标准剂量的非 CKD 参考人群的药物水平进行了比较:我们分析了 24 名患者的 143 种药物水平。首次测量药物浓度时的平均(标清)年龄为 64.7(15.9)岁(50% 为女性),随访时间的中位数(IQR)为 12.5(5.5 - 21)个月。阿哌沙班 2.5 毫克每日一次组和每日两次组的药物浓度中位数(IQR)分别为 54.4(< 40 - 72.1)纳克/毫升和 71.3(48.8 - 104.1)纳克/毫升(P < 0.001)。药物水平低于检测限的比例分别为 30%(2.5 毫克,每天一次)和 14%(2.5 毫克,每天两次)。只有给药组别(每天两次与每天一次)与较高的药物浓度有独立关联(P = 0.002)。随访结果未显示药物蓄积。药物浓度的第 95 百分位数未超过每天两次、每次 5 毫克的非慢性阻塞性肺病患者。出血(8 次)前的药物浓度中位数(IQR)高于未发生出血的药物浓度中位数(IQR):111.6(83.1 - 129.3)纳克/毫升对 54.8(< 40 - 77.1)纳克/毫升(P < 0.001)。在发生出血事件的患者中,86%的患者同时使用了抗血小板疗法,而在未发生出血事件的患者中,只有6%的患者同时使用了抗血小板疗法(P < 0.001):结论:药物监测是提高患者安全性的有效工具。尽管不存在目标范围,但药物水平的两个边缘(如低于可检测水平或超过参考人群的第95百分位数)可改善高度个体化的风险-效益分析决策。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Apixaban dosing in hemodialysis - can drug level monitoring mitigate controversies?

Background: 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.

Methods: 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.

Results: 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 95th 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).

Conclusions: 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 95th percentiles of reference populations) may improve decision-making in highly individualized risk-benefit analyses.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
BMC Nephrology
BMC Nephrology UROLOGY & NEPHROLOGY-
CiteScore
4.30
自引率
0.00%
发文量
375
审稿时长
3-8 weeks
期刊介绍: BMC Nephrology is an open access journal publishing original peer-reviewed research articles in all aspects of the prevention, diagnosis and management of kidney and associated disorders, as well as related molecular genetics, pathophysiology, and epidemiology.
期刊最新文献
Centre-level fluid management practices in the BISTRO trial and their lack of association with participant fluid status and blood pressure in non-anuric haemodialysis patients. Impact of COVID-19 on nephropathy in diabetes mellitus type-II patients: a systematic literature review and meta-analysis. Association between different proportions of crescents and the progression of IgA nephropathy (IgAN): a systematic review and meta-analysis. Decoy cells detected in the urine of a patient with complex karyotype Myelodysplastic neoplasms who underwent umbilical cord blood transplantation: a case report. Internal hernia following laparoendoscopic single site surgery: a case report.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1