基于FAERS数据库的VEGFR-TKIs相关高血压不良事件数据挖掘研究

Data mining for hypertension associated with VEGFR-TKIs:based on FAERS database

目的分析血管内皮生长因子受体(VEGFR)-酪氨酸激酶抑制剂(TKIs)相关高血压不良事件(AE)特点,比较不同VEGFR-TKIs相关高血压AE信号强度和发生时间。方法对2004年第一季度至2020年第四季度美国食品药品管理局不良事件报告系统(FAERS)数据库中VEGFR-TKIs相关高血压AE报告进行回顾性分析,通过报告比值比(ROR)法、英国药品和保健品管理局的综合标准(MHRA)法和信息成分(IC)法对VEGFR-TKIs相关高血压AE进行信号挖掘,采用My SQL Workbench和R软件对数据进行管理和可视化,同时对临床特征等数据信息进行分析。结果共获得11488份以9种VEGFR-TKIs为主要可疑药物的高血压AE报告。高血压AE报告中65岁及以上患者的占比最高(43.11%),舒尼替尼相关高血压报告比例最高(23.62%)。数据挖掘结果显示,9种VEGFR-TKIs均检出高血压AE信号,其中仑伐替尼的信号最强。高血压AE主要发生在VEGFR-TKIs治疗用药后30 d内。结论具有抗血管生成作用的VEGFR-TKIs相关高血压AE信号较强,临床用药过程中应密切监测血压,尤其是在患者开始服用VEGFR-TKIs治疗时应提醒其监测血压。

Objective To analyze the characteristics of hypertension adverse event(AE)associated with vascular endothelial growth factor receptor(VEGFR)-tyrosine kinase inhibitors(TKIs)and compare the hypertension AE signals and onset time among different VEGFR-TKIs.Methods A retrospective analysis of VEGFR-TKIs-associated hypertension AE reports in the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database from the first quarter of 2004 to the fourth quarter of 2020 was performed to detect the AE signs of VEGFR-TKIs-associated hypertension by the reporting odds ratio(ROR)method,composite criteria method of Medicines and Healthcare Products Regulatory Agency(MHRA)in the UK and information component(IC)method,and the data were managed and visualized by using MySQL Workbench and R soſtware,while information about the data such as clinical features was analyzed.Results A total of 11488 AE reports of hypertension associated with 9 VEGFR-TKIs as the primary suspected drugs were detected.The proportion of patients over 65 years old(43.11%)and the proportion of hypertension associated with sunitinib(23.62%)were the highest in AE reports of hypertension.9 VEGFR-TKIs were detected with hypertension related events signs.The signals of lenvatinib were the most strong among hypertension cases associated with 9 VEGFR-TKIs.AE of hypertension mostly occurred within 30 days after VEGFR-TKIs therapy.Conclusions The AE signals of hypertension associated with antiangiogenic TKIs were very intense.Blood pressure should be supervised more closely.It is of great significance that patients should be educated to conduct self-monitoring of blood pressure when starting VEGFR-TKIs treatment.