摘要
目的:评价国产缬沙坦的安全性不良事件及其影响因素。方法:本研究采用前瞻性队列研究设计,利用一项多中心随机对照试验(ESPRIT研究)2019年9月至2021年12月期间的药物处方和安全性监测数据,分析国产缬沙坦安全性不良事件的发生情况。利用多水平广义估计方程模型,探究用药情况及个体因素对安全性不良事件发生风险的影响。结果:本研究共纳入64303张包含国产缬沙坦的处方,共纳入8021例高血压患者。所有处方对应的患者平均年龄(64.5±7.1)岁,女性27015例(42.0%)。所有国产缬沙坦处方对应的患者中,446例(0.69%)发生了安全性不良事件;其中高钾血症和估算肾小球滤过率(eGFR)下降[eGFR<60 ml/(min·1.73 m^(2))且较用药前下降>30%]分别为75例(0.12%)和285例(0.44%)。纳入转归分析的62例发生高钾血症的患者中49例(79.0%)不需要停药即可恢复正常;发生eGFR下降的患者中,283例(99.3%)可逆。年龄≥70岁(RR=1.93,95%CI:1.43~2.60,P<0.001)、合并糖尿病(RR=1.32,95%CI:1.08~1.61,P=0.007)、开处方前血钾为5.1~5.5 mmol/L(RR=2.23,95%CI:1.49~3.34,P<0.001)、开处方前eGFR为60~89 ml/(min·1.73 m^(2))(RR=1.77,95%CI:1.45~2.15,P<0.001)均与安全性不良事件风险升高相关。与女性相比,男性发生安全性不良事件的风险较低(RR=0.79,95%CI:0.63~0.97,P=0.028)。结论:国产缬沙坦在我国无明显肾脏损害的高血压患者中安全性良好。定期监测血钾、eGFR,关注血钾处于正常高值、eGFR轻度下降的患者,尤其老年人、女性、合并糖尿病患者,可提高国产缬沙坦安全性。
Objectives:To examine the safety profile of domestic valsartan and factors associated with its safety.Methods:Based on the prescriptions and safety monitoring data collected in ESPRIT trial,a multi-center randomized controlled trial performed between September 2019 and December 2021,we designed a prospective cohort study to describe the incidence of safety adverse events related to domestic valsartan.Potential factors associated with risk of safety adverse events,such as patient characteristics,dosage,drug combination,were analyzed with a multi-level generalized estimating equation model.Results:A total of 8021 patients and 64303 valsartan prescriptions were included in this analysis.Mean age of patients was(64.5±7.1)years and 27015(42.0%)patients were female.The prescription-level incidence of the safety adverse events was 446(0.69%)patients.The incidence of hyperkalemia and estimated glomerular filtration rate(eGFR)slope was 75(0.12%)and 285(0.44%)patients,respectively.Among the patients with hyperkalemia,49(79.0%)patients of patients recovered without drug withdrawal.283(99.3%)patients of the eGFR slope was reversible.Subsequent analysis identified the following characteristics as independent risk factors for safety events:age 70 years or older(RR=1.93,95%CI:1.43-2.60,P<0.001);diabetes mellitus(RR=1.32,95%CI:1.08-1.61,P=0.007);serum potassium level between 5.1 to 5.5 mmol/L(RR=2.23,95%CI:1.49-3.34,P<0.001);eGFR level between 60 to 89 ml/(min·1.73 m^(2))(RR=1.77,95%CI:1.45-2.15,P<0.001).The male sex is an independent protective factor for safety events(RR=0.79,95%CI:0.63-0.97,P=0.028).Conclusions:Domestic valsartan exhibits satisfactory safety profile.Its safety profile can be improved by monitoring serum potassium and eGFR.More attention should be devoted to patients with high normal serum potassium or slightly decreased eGFR,particularly in diabetic,female,and aged patients.
作者
李艳
严小芳
李佳颖
葛金卓
张莉
李同社
李峰
管铮
李大庆
王海军
刘佳敏
李静
LI Yan;YAN Xiaofang;LI Jiaying;GE Jinzhuo;ZHANG Li;LI Tongshe;LI Feng;GUAN Zheng;LI Daqing;WANG Haijun;LIU Jiamin;LI Jing(State Key Laboratory of Cardiovascular Disease,NHC Key Laboratory of Clinical Research for Cardiovascular Medications,National Clinical Research Center for Cardiovascular Diseases,National Center for Cardiovascular Diseases and Fuwai Hospital,CAMS and PUMC,Beijing(100037),China)
出处
《中国循环杂志》
CSCD
北大核心
2023年第1期67-73,共7页
Chinese Circulation Journal
基金
科技部国家重点研发计划(2018YFC1312404、2018YFC1312400、2018YFC1312401)
中国医学科学院阜外医院国家心血管疾病临床医学研究中心自主课题资助(NCRC2021001)。
关键词
缬沙坦
安全性
高血压
高钾血症
估算肾小球滤过率
valsartan
safety
hypertension
hyperkalemia
estimated glomerular filtration rate
