基于美国FDA不良事件数据库的利伐沙班不良反应信号挖掘

吴圆圆 郑淑芬 钟诗龙

中圖分类号 R973+.2;R969.3 文献标志码 A 文章编号 1001-0408（2021）14-1764-06

DOI 10.6039/j.issn.1001-0408.2021.14.17

摘 要 目的：挖掘利伐沙班的药品不良反应（ADR）信号，为其临床安全合理使用提供参考。方法：基于美国FDA不良事件报告系统，采用报告比值比法和比例报告比法对FDA公共数据开放项目中于2008年9月-2020年12月上报的利伐沙班ADR报告进行数据挖掘，分析相关ADR报告并映射得到对应的系统器官分类（SOC）;同时，统计报告病例的性别、年龄、适应证等基本信息。结果与结论：共提取到相关ADR报告9 373 236例，其中以利伐沙班为伴随和怀疑药物的ADR报告有102 027例;共挖掘得到ADR信号883个，涉及系统器官27个。102 027例ADR报告中，女性（41 294例，占40.47%）与男性（41 071例，占40.26%）比例相当;年龄主要在>50～75岁（29 261例，占28.68%）和>75岁（21 470例，占21.04%）;上报年份主要集中在2018年（18 446例，占18.08%）;主要上报国家为美国（75 390例，占73.89%）;严重的ADR报告有35 046例（占34.35%），以住院或住院时间延长为主。利伐沙班ADR信号的SOC主要集中在血液和淋巴系统疾病、血管疾病、各类检查及神经系统疾病。在ADR报告数排序前20位的ADR首选术语中，除肺栓塞、急性肾损伤和心房颤动外，其余主要为出血相关的ADR，其中颅内出血是较为严重的ADR。当利伐沙班应用于房颤和预防脑血管意外时易引发颅内出血，当应用于肺栓塞、（深）静脉血栓和血栓形成预防时易引发肺栓塞，临床应密切关注。

关键词 利伐沙班;美国FDA不良事件报告系统;药品不良反应;信号挖掘;比例报告比法;报告比值比法

ADR Signal Mining of Rivaroxaban Based on FDA Adverse Event Reporting Database

WU Yuanyuan1，2，3，ZHENG Shufen2，3，ZHONG Shilong1，2，3（1. School of Biology and Biological Engineering， South China University of Technology， Guangzhou 510006， China; 2. Dept. of Pharmacy， Guangdong Provincial Peoples Hospital， Guangzhou 510080， China; 3. Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention and Treatment， Guangdong Provincial Peoples Hospital， Guangzhou 510080， China）

ABSTRACT   OBJECTIVE： To excavate the ADR signals of rivaroxaban and provide reference for its safe and rational use in clinic. METHODS： Based on FDA adverse event reporting system （FAERS）， the ADRs of rivaroxaban reported from September 2008 to December 2020 in FDAs Open Data Program were mined using ratio of reports to odds （ROR） and proportional report ratio （PRR）. The related ADRs were analyzed， and the corresponding system organ classification （SOC） was mapped. At the same time， the basic information such as gender， age and indications of the patients were statistically reported. RESULTS & CONCLUSIONS： Among 9 373 236 ADR reports extracted， 102 027 ADR reports with rivaroxaban as concomitant and suspected drug were obtained; 883 ADR signals were mined， involving 27 systems. Among 102 027 reports， the proportion of female patients （41 294 cases， 40.47%） was similar to that of male patients （41 071 cases， 40.26%）. The patients were mainly >50 to 75 years old （29 261 cases， 28.68%） and >75 years old （21 470 cases， 21.04%）. The reporting year was mainly in 2018 （18 446 cases， 18.08%）; main reporting country was the United States （75 390 cases， 73.89%）; there were 35 046 cases （34.35%） of severe ADR reports， mainly involving hospital or prolonged hospital stay. The SOC of rivaroxaban ADR singal mainly focused on diseases of the blood and lymphatic system， vascular diseases， various types of examination and nervous system diseases. Among top 20 preferred terms of ADRs with the highest frequency， except for pulmonary embolism， acute kidney injury and atrial fibrillation， the rest were mainly bleeding related ADRs， of which intracranial hemorrhage was the more serious ADR. Intracranial hemorrhage may occur when rivaroxaban is used for the prevention of atrial fibrillation and cerebrovascular accidents， and pulmonary embolism may occur when rivaroxaban is used for the prevention of pulmonary embolism， （deep） venous thrombosis and thrombosis. Great importance should be paid on it.

KEYWORDS   Rivaroxaban; FDA adverse event reporting system; Adverse drug reactions; Signal mining; Ratio of reports to odds; Proportional report ratio

利伐沙班（rivaroxaban）是一种口服、直接的Ⅹa因子抑制剂，具有高度选择性，可竞争性地与Ⅹa因子的活性位点结合，是新型口服抗凝药物（NOACs）的代表药物[1]。利伐沙班……