基于FAERS的替格瑞洛及氯吡格雷相关出血事件信号挖掘

Signal Mining of Hemorrhage Events Related to Ticagrelor and Clopidogrel Based on FAERS Database

目的为替格瑞洛及氯吡格雷的临床合理应用提供指导与依据。方法利用美国食品和药物管理局(FDA)不良事件报告系统(FAERS)获取替格瑞洛和氯吡格雷从上市起至2021年9月30日的药品不良事件(ADE)报告数据,采用标准MedDRA查询(SMQ)检索其中的出血事件报告,采用报告比值比(ROR)法进行信号挖掘。结果分别获得两药相关出血报告3326例和25538例,严重不良事件(SAE)发生率均较高(66.36%,67.22%),均以住院/住院时间延长为主(40.56%,45.83%)。替格瑞洛[ROR=4.02,95%CI(3.86,4.18)]出血信号值低于氯吡格雷[ROR=6.32,95%CI(6.22,6.42)]。替格瑞洛相关出血事件涉及17个系统器官分类(SOC),85个可疑信号;氯吡格雷涉及18个SOC,198个可疑信号。出血事件多分布于胃肠系统(33.98%,43.08%)以及血管与淋巴管系统(20.42%,14.03%)。结论替格瑞洛与氯吡格雷均可诱发多个系统的出血事件,其中胃肠系统较多见,临床应加强对此两种药物的出血事件监护。

Objective To provide guidance and basis for the rational clinical application of ticagrelor and clopidogrel.Methods The adverse drug event(ADE)report data of ticagrelor and clopidogrel from the time of marketing to September 30,2021 were obtained through the Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS),and the hemorrhage event reports were retrieved by the standard MedDRA query(SMQ),and the reported odds ratio(ROR)method was used for signal mining.Results A total of 3326 and 25538 hemorrhage event reports related to the two drugs were obtained respectively.The incidence rates of serious adverse events(SAE)of the two drugs were high(66.36%,67.22%),and most of them were caused by hospitalization/extended length of stay(40.56%,45.83%).The hemorrhage signal value of ticagrelor[ROR=4.02,95%CI(3.86,4.18)]was lower than that of clopidogrel[ROR=6.32,95%CI(6.22,6.42)].Ticagrelor-related hemorrhage events involved 17system organ classification(SOC)and 85 suspicious signals.Clopidogrel involved 18 SOC and 198 suspicious signals.Hemorrhage events were mainly distributed in the gastrointestinal system(33.98%,43.08%)and the vascular and lymphatic system(20.42%,14.03%).Conclusion Both ticagrelor and clopidogrel may induce hemorrhage events in multiple systems,of which gastrointestinal system is more common.The monitoring of hemorrhage events of these two drugs should be strengthened in the clinic.