口服抗凝药致肾损伤风险:基于美国FDA不良事件报告系统数据库的研究  

Risk of kidney injury due to oral anticoagulants:a study based on FDA Adverse Event Reporting System database

作　　者：彭文星[1] 陈国权 丁征 Peng Wenxing;Chen Guoquan;Ding Zheng(Department of Pharmacy,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China;Department of Pharmacy,Affiliated Jinhua Hospital,Medical College of Zhejiang University,Zhejiang Province,Jinhua 321001,China;Department of Pharmacy,Fuwai Hospital,Chinese Academy of Medical Sciences,Beijing 100037,China)

机构地区：[1]首都医科大学附属北京安贞医院药事部,北京100029 [2]浙江大学医学院附属金华医院药学部,金华321001 [3]中国医学科学院阜外医院药剂科,北京100037

出　　处：《药物不良反应杂志》2025年第1期11-16,共6页Adverse Drug Reactions Journal

基　　金：北京慢性病防治与健康教育科研项目(BJMB0012022028007)。

摘　　要：目的挖掘不同口服抗凝药物(OAC)在不同人群中引起急性肾损伤(AKI)的风险信号,为临床使用OAC提供参考。方法检索美国食品药品管理局(FDA)不良事件报告系统(FAERS)数据库2004年第1季度至2023年第3季度收到的OAC与非OAC致AKI的报告,采用报告比值比(ROR)法和贝叶斯置信传播神经网络(BCPNN)法,分析上述药物与患者发生AKI的关系。当目标药物发生目标不良事件的报告数量≥3且ROR的95%置信区间(CI)下限>1或信息成分(IC)的95%CI下限(IC025)>0时,提示目标药物与目标不良事件之间的相关性有统计学意义。结果共收集到OAC相关AKI报告12402份,包括华法林1313份,达比加群3086份,利伐沙班4730份,阿哌沙班2918份,艾多沙班365份;非OAC相关AKI报告454378份。对OAC的整体分析结果显示,OAC导致AKI的ROR值(95%CI下限)为1.791(1.759),IC值(IC025)为0.813(0.787)。对OAC单一药物致AKI事件的分析结果显示,华法林、达比加群、利伐沙班、阿哌沙班和艾多沙班均具有引起AKI的风险,其ROR值(95%CI下限)分别为1.220(1.156)、2.386(2.302)、2.044(1.986)、1.375(1.326)、3.003(2.706),其IC值(IC025)分别为0.284(0.204)、1.231(1.178)、1.010(0.968)、0.452(0.399)、1.560(1.407),其中艾多沙班ROR值和IC值最高,华法林的ROR值和IC值最低。亚组分析结果显示,在<18岁亚组中,华法林和利伐沙班均未显示具有引起AKI的风险;ROR法未显示达比加群具有引起AKI的风险,而BCPNN法显示其有。在18~45岁亚组中,2种挖掘方法均显示阿哌沙班不具有引起AKI的风险,其他OAC均显示有。在45~64岁亚组中,所有OAC均显示具有引起AKI的风险。在≥65岁亚组中,华法林和阿哌沙班均具有引起AKI的风险。性别亚组分析结果显示,2种挖掘方法均显示华法林在男性中具有引起AKI的风险;所有OAC均显示在女性中具有引起AKI的风险。结论OAC有引起AKI的风险,其中艾多沙班风险最大,华法林最低;不同OAC在不同年龄�Objective To mine the risk signal of acute kidney injury(AKI)induced by different oral anticoagulant drugs(OACs)in various populations and provide a reference for clinical use of OACs.Methods Reports of AKI induced by OACs and non-OACs in the US Food and Drug Administration Adverse Event Reporting System database from the 1st quarter of 2004 to the 3rd quarter of 2023 were collected.The relationship between the drugs mentioned above and the AKI in patients were analyzed by methods of reporting odds ratio(ROR)and Bayesian confidence propagation neural network(BCPNN).When the number of reports of the target adverse event(AE)for the target drug was≥3,and the lower limit of the 95%confidence interval(CI)of ROR was>1 or the lower limit of the 95%CI of the information component(IC 025)was>0,it indicated a statistically significant association between the target drug and the target AE.Results A total of 12402 AKI reports related to OACs were collected,including 1313 for warfarin,3086 for dabigatran,4730 for rivaroxaban,2918 for apixaban,and 365 for edoxaban;454378 AKI reports were related to non-OACs.The overall analysis of OACs showed an ROR(lower limit of 95%CI)of 1.791(1.759)and an IC(IC 025)of 0.813(0.787)for AKI caused by OACs.Analysis of individual OACs showed that warfarin,dabigatran,rivaroxaban,apixaban,and edoxaban all posed risks for AKI,with ROR(lower limit of 95%CI)of 1.220(1.156),2.386(2.302),2.044(1.986),1.375(1.326),3.003(2.706),respectively,and IC(IC 025)of 0.284(0.204),1.231(1.178),1.010(0.968),0.452(0.399),1.560(1.407),respectively.Edoxaban had the highest ROR and IC values,while warfarin had the lowest.Subgroup analysis showed that in the<18 years subgroup,neither warfarin nor rivaroxaban showed a risk of AKI;the ROR method did not show dabigatran to have a risk of AKI,but the BCPNN method did.In the 18-45 years subgroup,both methods showed that apixaban did not have a risk of AKI,while all other OACs did.In the 45-64 years subgroup,all OACs showed a risk of AKI.In the≥65 years subgroup,warfarin a

关 键 词：Xa因子拮抗剂 急性肾损伤 数据挖掘 药物不良事件报告系统 抗凝药物相关肾病 口服抗凝药物 直接口服抗凝药物 

分 类 号：R69[医药卫生—泌尿科学]