致心律失常不良反应药物信号的检测与评价

Detection and evaluation of drug signals of arrhythmic adverse reactions

目的检测和评价致心律失常药品不良反应(adverse drug reaction,ADR)药物信号,为临床安全用药提供参考。方法收集2004年第1季度至2020年第4季度美国食品药品监督管理局不良事件报告系统自发呈报系统中接收到的致心律失常ADR信号,采用比例报告比法(proportional reporting ratios,PRR)和报告比值比法(proportional reporting odds ratio,ROR)对进行信号检测,分析ADR报告中对应病人的基本信息(包括性别、年龄、上报年份、上报国家、严重ADR)和安全警告信号。结果收集到的65536份ADR报告中,排除重复,保留首要怀疑药物和伴随药物的ADR报告有20401份。除性别未知和年龄缺失的ADR报告外,纳入报告病人的性别分布女性稍高于男性(9918比8401),年龄范围50~75岁比例较高,其余分布较均衡,上报数量最多的年份分别是2005年、2011年、2012年、2018年和2019年,主要上报国家为美国、德国等。严重的ADR报告有11158份(占54.7%),以“住院或住院时间延长”为主,导致死亡占16.88%。共挖掘得到ADR信号478个,累及心血管系统(122个)、内分泌系统(48个)、抗精神病(43个)、神经系统(32个)、抗感染(22个)、呼吸系统(22个)、血液系统(17个)、抗肿瘤(16个)等19个系统用药。致心律失常ADR信号频数排序前10位的药物分别为罗非考昔(频数1795)、罗非昔布(频数1792)、对乙酰氨基酚(频数1393)、左甲状腺素(频数912)、美托洛尔(频数879)、缬沙坦(频数805)、罗格列酮(频数798)、丙氧酚(频数776)、呋塞米(频数687)、氢氯噻嗪(频数635)。头孢噻吩信号强度值最高,对乙酰氨基酚次之。结论心血管系统、抗精神病、神经系统、抗感染、呼吸系统、血液系统、抗肿瘤等用药致心律失常安全风险较高。用药时应提高警惕,早期发现及时停药,并积极予以对症治疗,降低药源性不良反应的危害。

Objective To detect and evaluate the drug signals of arrhythmic adverse drug reaction(ADR),and to provide reference for clinical safe drug use.Methods Arrhythmogenic ADR signals received from the spontaneous notification system of the US FDA Adverse Event Reporting System from the first quarter of 2004 to the fourth quarter of 2020 were collected.Proportional reporting odds ratio(ROR)and proportional reporting Odds ratio(PRR)were used to detect signals.The basic information(including gender,age,re‐porting year,reporting country,serious ADR)and safety warning signals of corresponding patients in ADR reports were analyzed.Re⁃sults Of the 65536 ADR reports collected,there were 20401 ADR reports that retained the primary suspected drug and concomitant drug excluding duplication.Except for the ADR reports with unknown gender and age loss,the gender distribution of included patients was slightly higher in females than in males(9918 vs.8401),and the proportion of age range from 50 to 75 years old was relatively high.The rest of the distribution was more balanced.The most reported years were 2005,2011,2012,2018 and 2019,and the main re‐porting countries were the United States and Germany.There were 11158 serious ADR reports(54.7%),mainly"hospitalization or pro‐longed hospitalization",16.88%in death.A total of 478 ADR signals were obtained,involving 19 systems such as cardiovascular sys‐tem(122),endocrine system(48),antipsychotic system(43),nervous system(32),anti-infective system(22),respiratory system(22),blood system(17),and anti-tumor system(16).The top 10 drugs in the ranking of arrhythmia induced ADR signal frequency were rofe‐coxib(frequency 1795),rofecoxib(frequency 1792)and acetaminophen(frequency 1393),levothyroxine(frequency 912),metoprolol(frequency 879),valsartan(frequency 805),rolitazone(frequency 798),propofol(frequency 776),furosamide(frequency 687),hydro‐chlorothiazide(frequency 635).The signal intensity of cephalothiophene was the highest,followed by acetaminophen.Conclusions Cardiovascular system,antipsychotic system,nervous system,anti-infective system,respiratory system,blood system,anti-tumor drug induced arrhythmia safety risk is higher.When taking medicine,we should be vigilant,early detection and timely discontinue medi‐cine,and actively give symptomatic treatment to reduce the harm of drug-induced adverse reactions.