摘要
目的:评价国产氢氯噻嗪的安全性及其影响因素。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-2022年1月的处方和安全性监测数据,纳入心血管疾病高危风险的高血压患者,分析国产氢氯噻嗪安全性复合事件的发生情况。利用广义估计方程模型,探究用药情况及个体因素对其发生风险的影响。结果:研究共纳入10179例次处方,对应1851例患者,平均年龄为(65.1±7.1)岁,40.7%为女性。氢氯噻嗪安全性复合事件发生率为4.2%,其中定期监测发现的低钾血症(2.5%)和低钠血症(1.6%)最常见。中重度低钾血症和中重度低钠血症发生率分别为0.07%和0.11%。无需停药,69.4%低钾血症和73.2%低钠血症可恢复正常。处方前血钾3.5~3.9 mmol/L(RR=1.45,95%CI:1.20~1.75)和血钠135~139 mmol/L(RR=1.43,95%CI:1.17~1.74)、非每天摄入新鲜水果(RR=1.32,95%CI:1.04~1.67)与发生安全性复合事件风险升高相关。结论:国产氢氯噻嗪安全性良好。定期监测血钾、血钠,关注血钾、血钠处于正常低值和不能每天摄入新鲜水果的患者,采取必要的预防措施,可降低安全性事件发生风险。即使发生低钾血症或低钠血症,大多数患者减低剂量或经补钾、补钠治疗后仍可继续使用氢氯噻嗪。
Objective: To examine the profile of domestic hydrochlorothiazide safety and identify any associatedfactors. Methods: Based on data collected in ESPRIT which was a multi-center randomized controlled trial between September 2019 and January 2022, we designed a prospective cohort study and enrolled hypertensive patients with high risk of cardiovascular disease to describe the incidence of a composite of safety events related to hydrochlorothiazide. We then examined potential factors associated with the risk of composite safety events, such as patient characteristics, dosage, and drug combination by using a generalized estimating equation model. Results: A total of 1851 patients and 10179 prescriptions were included in our analyses. Patients aged(65.1±7.1) years;40.7% were female. The prescription-level incidence of the composite safety events was 4.2%, with the most common components being hypokalemia(2.5%) or hyponatremia(1.6%). The incidence of moderate to severe hypokalemia and moderate to severe hyponatremia was 0.07% and 0.11%, respectively. Among the patients with hypokalemia, 69.4% of patients recovered without drug withdrawal, the proportion in the patients with hyponatremia was 73.2%. Subsequent analyses identified the independent risk factors for incident composite safety events;serum potassium level between 3.5 to 3.9 mmol/L(RR=1.45, 95%CI: 1.20-1.75);serum sodium between 135 to 139 mmol/L(RR=1.43, 95%CI: 1.17-1.74);non-daily intake of fresh fruits(RR=1.32, 95%CI: 1.04-1.67). Conclusion: Hydrochlorothiazide exhibited a satisfying safety profile. It would further improve the safety to monitor blood potassium and sodium and take necessary preventive measures, particularly in the patients with a lower-normal level of blood potassium or sodium, or in those non-daily taking fresh fruits. Even if hypokalemia or hyponatremia occurs, most patients can still use hydrochlorothiazide after reducing the dose or treating with potassium or sodium supplement.
作者
李佳颖
李艳
刘佳敏
严小芳
衣少伟
董玉梅
梁林炬
王志敏
王晓飞
郝世国
李静
LI Jiaying;LI Yan;LIU Jiamin;YAN Xiaofang;YI Shaowei;DONG Yumei;LIANG Linju;WANG Zhimin;WANG Xiaofei;HAO Shiguo;LI Jing(NHC Key Laboratory of Clinical Research for Cardiovascular Medications,National Clinical Research Center for Cardiovascular Diseases,State Key Laboratory of Cardiovascular Disease,Fuwai Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100037,China;Department of Cardiology,Jining No.1 People's Hospital;Cardiovascular Center,Qingdao Fuwai Cardiovascular Hospital;Department of Outpatients,Health Care Service Center of Wenxi County;Department of Cardiology,The Second People's Hospital of Liaocheng;General Clinic,Qingdao Huangdao District Yinzhu Street East Lou Road Community Health Service Center;Department of Cardiology,Alxa League Central Hospital)
出处
《临床心血管病杂志》
CAS
北大核心
2022年第12期994-1000,共7页
Journal of Clinical Cardiology
基金
国家科技部国家重点研发计划(No:2018YFC1312400、2018YFC1312401、2018YFC1312404)
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(No:NCRC2021001)。
关键词
高血压
安全性
氢氯噻嗪
低钾血症
低钠血症
hypertension
safety
hydrochlorothiazide
hypokalemia
hyponatremia
