基于数据挖掘技术研究质子泵抑制剂与贫血相关的不良事件信号

Data Mining-based Techniques to Study the Adverse Event Signals Associated with Proton Pump Inhibitors and Anemia

目的通过数据挖掘和评价的方法研究质子泵抑制剂(Proton pump inhibitors,PPIs)与贫血相关事件的不良反应事件(Adverse drug events,ADE),为临床合理用药提供参考。方法提取美国不良事件报告系统(FAERS)中奥美拉唑、泮托拉唑、兰索拉唑、雷贝拉唑、艾司奥美拉唑、右兰索拉唑6种PPI药物与贫血相关的不良反应,应用ROR(Reporting odds ratio,ROR)及PRR(Proportional reporting ratio,PRR)两种方法进行信号分析,当同时满足ROR及PRR时,提示生成一个可疑信号。结果通过对年龄及性别的统计分析,肾性贫血及恶性贫血多分布于18~60岁患者,溶血性贫血、缺铁性贫血、正常细胞贫血及再生障碍性贫血主要分布在61~85岁患者,总的发生贫血事件以女性较男性多。信号检测结果显示,肾性贫血在6种PPI制剂中均能生成一个可疑信号;缺铁性贫血可在泮托拉唑、雷贝拉唑、兰索拉唑、奥美拉唑、艾司奥美拉唑中生成中生成一个可疑信号;溶血性贫血可在泮托拉唑、艾司奥美拉唑及雷贝拉唑中生成一个可疑信号;再生障碍性贫血可在兰索拉唑、泮托拉唑、艾司奥美拉唑中生成一个可疑信号;恶性贫血在泮托拉唑、艾司奥美拉唑、奥美拉唑、兰索拉唑中生成可疑信号;正常细胞性贫血可在泮托拉唑、艾司奥美拉唑、奥美拉唑中生成可疑信号。结论PPI制剂可能会导致患者贫血的发生,常见的贫血类型为肾损伤性贫血及缺铁性贫血,临床实践过程中应关注特殊人群,如肾损伤及营养缺乏患者同时使用PPI制剂的贫血情况,保障患者的安全用药。

OBJECTIVE To study the adverse drug events(ADEs)of proton pump inhibitors(PPIs)with anemia-related events by data mining and evaluation methods,and to provide reference for rational clinical use of drugs.METHODS The adverse events associated with anemia of six PPIs,namely omeprazole,pantoprazole,lansoprazole,rabeprazole,esomeprazole and dexlansoprazole,were extracted from the American Adverse Event Reporting System(FAERS),and the ROR(Reporting odds ratio,ROR)and PRR(Proportional reporting ratio,PRR)were applied.When both ROR and PRR were satisfied,it was suggested that a suspicious signal was generated.RESULTS By statistical analysis of age and gender,renal anemia and pernicious anemia were mostly distributed in patients aged 18-60 years,and hemolytic anemia,iron deficiency anemia,normocytic anemia and aplastic anemia were mainly distributed in patients aged 61-85 years,and the total occurrence of anemia events was more in females than in males.The signal detection results showed that renal anemia could generate a suspicious signal in all six PPI preparations;iron deficiency anemia could generate a suspicious signal in pantoprazole,rabeprazole,lansoprazole,omeprazole,and estramiprazole;hemolytic anemia could generate a suspicious signal in pantoprazole,estramiprazole,and rabeprazole;aplastic anemia could generate a suspicious signal in lansoprazole,pantoprazole,estramiprazole;pernicious anemia may generate a suspicious signal in pantoprazole,estramiprazole,omeprazole,lansoprazole;normocytic anemia may generate a suspicious signal in pantoprazole,estramiprazole,omeprazole.CONCLUSION PPI agents may lead to the development of anemia in patients,and the common types of anemia are renal injury anemia and iron and zinc deficiency anemia,and this study may provide a reference for the rational clinical use of the drugs.