基于FDA不良事件报告系统数据库的细胞周期蛋白依赖性激酶4/6抑制剂心血管不良事件信号挖掘

Data-mining of cardiovascular adverse events signals for cyclin-dependent kinase 4/6 inhibitors based on FDA Adverse Event Reporting System database

目的基于美国FDA不良事件报告系统(FAERS)数据库,挖掘细胞周期蛋白依赖激酶4/6(CDK4/6)抑制剂发生心血管不良事件(AEs)的信号,为临床安全用药提供参考。方法从FAERS数据库提取自2015—2023年哌柏西利、瑞波西利和阿贝西利心血管AEs报告数据,根据标准国际医学用语词典(MedDRA)分析查询入门指南(SMQ),将心血管AEs分为9个狭义的SMQ类别,采用报告比值比(ROR)法对信号进行挖掘分析。结果共收集到与CDK4/6抑制剂心血管AE的报告7571份,其中哌柏西利4437份,瑞波西利2450份,阿贝西利684份,共涉及患者6417例。在SMQ层面,哌柏西利未检测到阳性信号,瑞波西利检测到心律失常(ROR=2.32;95%CI:2.17~2.47)和QT间期延长的阳性信号(ROR=6.14;95%CI:5.75~6.77),阿贝西利检测到栓塞和血栓事件的阳性信号(ROR=1.63;95%CI:1.49~1.78);在首选术语层面,3种CDK4/6抑制剂均发现了血栓形成、肺栓塞和肺水肿的阳性信号。结论不同CDK4/6抑制剂心血管AEs的临床表现及发生强度存在差异。医师使用CDK4/6抑制剂前,需充分评估患者生理状态,根据药物AEs的特点进行个体化用药选择和AEs监测。

Objective To detect cardiovascular adverse events(AEs)signals of cyclin‑dependent kinase 4/6(CDK4/6)inhibitors,using the U.S.FDA Adverse Event Reporting System(FAERS)database,and to provide reference for clinically safe use of drugs.Methods Based on the FAERS database,adverse events(AE)reports about cardiovascular related to palbociclib,ribociclib,and abemaciclib were collected from 2015 to 2023.Cardiovascular AE was grouped into nine narrow categories using the Standardized Medical Dictionary for Regulatory Activities(MedDRA)Queries(SMQ).The AE signals were mined and analyzed with reporting odds ratio(ROR).Results A total of 7571 reports of cardiovascular AE related to CDK4/6 inhibitors were collected,including 4437 reports for palbociclib,2450 reports for ribociclib,and 684 reports for abemaciclib,involving 6417 patients.Based on SMQ,palbociclib did not detect positive signal,while ribociclib detected positive signal for cardiac arrhythmias(ROR=2.32,95%CI:2.17 to 2.47)and QT prolongation(ROR=6.14,95%CI:5.75 to 6.77),and abemaciclib detected embolic(ROR=1.63,95%CI:1.49 to 1.78)and thrombotic events.At the preferred terms level,all 3 kinds of CDK4/6 inhibitors caused positive signals for thrombosis,pulmonary embolism,and pulmonary oedema.Conclusion The clinical features and intensity of cardiovascular AE were different among CDK4/6 inhibitors.Clinicians must fully assess the patient's physiological status before using CDK4/6 inhibitors,and conduct individualized drug selection and monitoring according to the characteristics of drug AE.