基于美国FAERS的5-氟尿嘧啶和卡培他滨致心脏毒性的风险分析

Analysis of the risks of cardiotoxicity induced by 5-FU and capecitabine based on FAERS database

目的基于美国FDA药品不良事件报告系统(Food and Drug Administration Adverse Event Reporting System,FAERS),分析5-氟尿嘧啶(5-Fluorouracil,5-FU)和卡培他滨相关心脏毒性的特点。方法提取FAERS系统2004年1月至2022年9月5-FU和卡培他滨所致心脏不良事件的信息,采用报告比值比法(Reporting odds ratio,ROR)和比例报告比值比法(Proportional reporting ratio,PRR)进行联合检验,确定风险信息。结果基于FAERS数据库的分析,在5-FU和卡培他滨引起的不良事件中,心脏相关不良事件构成比分别为4.01%、2.11%。与数据库的背景药物相比,5-FU引起的射血分数降低、心脏假性动脉瘤、心功能不全、心肌病、心源性休克、心包炎/积液、心电图异常、心脏血栓形成、心绞痛、心室疾病、胸痛、二尖瓣关闭不全都产生了阳性信号;卡培他滨发生心律失常、心肌病、心电图异常、心功能不全、心源性休克、心力衰竭的风险也显著升高。上述不良反应大部分与说明书和其他文献报道的相似,但5-FU引起的心脏假性动脉瘤、二尖瓣关闭不全未见报道。结论基于FAERS数据库的分析,临床在使用5-FU和卡培他滨时,应注意对心脏相关症状、体征、心电图、超声心动图等进行定期监测,及时发现和处理心脏不良反应。

Objective To analyze the risks of cardiotoxicity induced by 5-fluorouracil(5-FU)and capecitabine based on Food and Drug Administration Adverse Event Reporting System(FAERS).Methods The reports on the adverse events induced by 5-FU and capecitabine from January 2004 to September 2022 were extracted from the FAERS database.The reporting odds ratio(ROR)and the proportional reporting ratio(PRR)methods were used to mine the signals.Results Based on FAERS database,of all adverse events caused by 5-FU and capecitabine,4.01%and 2.11%were cardiotoxicity.Compared with other drugs in the database,the decreased ventricular ejection fraction,cardiac pseudoaneurysm,cardiac dysfunction,cardiomyopathy,cardiogenic shock,pericarditis/pericardial effusion,abnormal electrocardiogram,intracardiac thrombosis,angina,cardiac ventricular disorder,chest pain and mitral valve incompetence caused by 5-FU produced positive signal,and the risks of abnormal heart rate,cardiomyopathy,abnormal electrocardiogram,cardiac dysfunction,cardiogenic shock and cardiac failure caused by capecitabine were also higher.Most of them were similar to those reported in the instructions and other literatures,but the cardiac pseudoaneurysm and mitral valve incompetence caused by 5-FU was first reported.Conclusion Based on FAERS database,the clinicians should pay attention to the regular monitoring of cardiac-related symptoms,signs,ECG,echocardiogram and so on when applying 5-FU and capecitabine,in order to recognize and manage cardiotoxicity in time.