基于美国FAERS数据库的3种新型口服抗凝血药的风险信号挖掘

Risk Signal Mining of Three New Oral Anticoagulants Based on FDA Adverse Event Reporting System Database

目的:利用大数据样本分析,挖掘3种新型口服抗凝血药达比加群酯、利伐沙班、阿哌沙班的风险信号,为临床合理用药提供参考。方法:基于美国食品药品监督管理局不良事件报告系统(FAERS)数据库,利用OpenVigil 2.1平台,提取2004年第1季度至2021年第3季度的报告,采用报告比值比法(ROR)和比例报告比值法(PRR)进行信号挖掘。根据《国际医学用语词典》(25.0版)中的首选语(PT)和系统器官分类(SOC)对风险信号进行描述分类。结果:分别检索到达比加群酯、利伐沙班、阿哌沙班的药品不良事件报告54932、112642、108850份。达比加群酯、利伐沙班、阿哌沙班发生例数排序居第1位的药品不良反应分别为胃肠出血(PRR=28.31,ROR=32.01)、胃肠出血(PRR=46.45,ROR=54.47)、出血(PRR=6.09,ROR=6.25),信号强度排序居第1位的药品不良反应分别为胃液潜血阳性(PRR=66.55,ROR=66.56)、出血性动静脉畸形(PRR=689.45,ROR=692.06)、脊髓蛛网膜下腔出血(PRR=50.58,ROR=50.59)。此外,利伐沙班可能导致急性肾损伤(发生例数排序居第10位),阿哌沙班可能导致肾功能损害(发生例数排序居第9位)、听觉减退(发生例数排序居第10位)和听觉障碍(信号强度排序居第7位),药品说明书均未提及,应予以关注。总体上,3种新型口服抗凝血药的出血风险发生率为利伐沙班>达比加群酯>阿哌沙班。结论:在使用达比加群酯、利伐沙班、阿哌沙班时,需重点关注出血风险,同时需关注利伐沙班和阿哌沙班新的风险信号。

OBJECTIVE:To mine the risk signals of three new oral anticoagulants such as dabigatran etexilate,rivaroxaban and apixaban based on big data sample analysis,so as to provide reference for rational clinical drug use.METHODS:Based on the FDA Adverse Event Reporting System(FAERS)database,OpenVigil 2.1 platform was used to extract reports from the 1st quarter of 2004 to the 3rd quarter of 2021.Reporting odds ratio(ROR)and proportional reporting ratio(PRR)were used for signal mining.The risk signals were described and classified according to the preferred terms(PT)and systematic organ classification(SOC)in the MedDRA(Edition 25.0).RESULTS:A total of 54932,112642,and 108850 adverse drug event reports were retrieved for dabigatran etexilate,rivaroxaban and apixaban,respectively.Adverse drug reactions with the first number of cases of dabigatran etexilate,rivaroxaban and apixaban were respectively gastrointestinal haemorrhage(PRR=28.31,ROR=32.01),gastrointestinal haemorrhage(PRR=46.45,ROR=54.47),and haemorrhage(PRR=6.09,ROR=6.25).Adverse drug reactions with the first signal intensity were gastric occult blood positive(PRR=66.55,ROR=66.56),haemorrhagic arteriovenous malformation(PRR=689.45,ROR=692.06),and spinal subarachnoid haemorrhage(PRR=50.58,ROR=50.59).Meanwhile,rivaroxaban may lead to acute kidney injury(the 10th ranked by occurrence),apixaban may lead to renal impairment(the 9th ranked by occurrence)and hypoacusis(the 10th ranked by occurrence)and auditory disorder(the 7th ranked by signal strength),which were not mentioned in the drug instructions and should be taken into account.The overall incidence of bleeding risk for the three new oral anticoagulants was rivaroxaban>dabigatran etexilate>apixaban.CONCLUSIONS:Dabigatran etexilate,rivaroxaban and apixaban need to be used with a focus on bleeding risk,and new risk signals for rivaroxaban and apixaban need to be followed.