苯磺酸氨氯地平联合氯沙坦钾治疗原发性轻、中度高血压患者的疗效和安全性:一项随机、双盲、多中心、析因临床研究  

Efficacy and safety of amlodipine besylate combined with losartan potassium in patients with mild to moderate essential hypertension:a randomized,double-blind,multicentric,factorial study

作　　者：袁洪[1] 姚朱华[2] 张德莲[3] 梅霞 李馨 赵水平[6] 张国刚[7] 赵秀丽[8] 林玲[9] 朱红[10] 刘先霞[11] 王浩宇 苏海[13] 张抒扬[14] YUAN Hong;YAO Zhuhua;ZHANG Delian;MEI Xia;LI Xin;ZHAO Shuiping;ZHANG Guogang;ZHAO Xiuli;LIN Ling;ZHU Hong;LIU Xianxia;WANG Haoyu;SU Hai;ZHANG Shuyang(Department of Cardiology,Clinical Pharmacology Center,The Third Xiangya Hospital of Central South University,Changsha,Hunan 410013,China;Department of Cardiology,Tianjin Union Medical Center;Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Hypertension Institute;Department of Cardiology,Chongqing People's Hospital;Department of Cardiology,Chongqing Red Cross Society Hospital;Department of Cardiology,The Second Xiangya Hospital of Central South University;Department of Cardiology,Xiangya Hospital Central South University;Department of Cardiology,Beijing Tongren Hospital,Capital Medical University;Department of Cardiology,Hainan Third People's Hospital;Department of Cardiology,The Affiliated Hospital of Xuzhou Medical University;Department of Cardiology,The Second Affiliated Hospital of Hainan Medical College;Department of Cardiology,Nanchong Central Hospital;Department of Cardiology,The Second Affiliated Hospital of Nanchang University;Department of Cardiology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College)

机构地区：[1]中南大学湘雅三医院心内科临床药理中心,湖南长沙410013 [2]天津市人民医院心内科 [3]新疆维吾尔自治区人民医院高血压科 [4]重庆市人民医院心内科 [5]重庆市红十字会医院心内科 [6]中南大学湘雅二医院心内科 [7]中南大学湘雅医院心内科 [8]首都医科大学附属北京同仁医院心内科 [9]海南省第三人民医院心内科 [10]徐州医学院附属医院心内科 [11]海南医学院第二附属医院心内科 [12]南充市中心医院心内科 [13]南昌大学第二附属医院心内科 [14]中国医学科学院北京协和医院心内科

出　　处：《中华高血压杂志（中英文）》2024年第3期271-282,共12页Chinese Journal of Hypertension

摘　　要：目的评估苯磺酸氨氯地平联合氯沙坦钾治疗原发性轻、中度高血压患者的疗效和安全性,并根据析因研究设计,探索两种药物对于降压效果影响的交互作用。方法本研究为一项为期8周、随机、双盲、析因设计、Ⅱ期、多中心临床研究。纳入299例原发性轻、中度高血压患者,并按照1∶1∶1∶1∶1∶1的比例随机分为6组:A组患者接受苯磺酸氨氯地平5mg模拟剂、氯沙坦钾50mg模拟剂和氯沙坦钾100mg模拟剂治疗;B1组患者接受氯沙坦钾50mg、苯磺酸氨氯地平5mg模拟剂、氯沙坦钾100mg模拟剂;B2组患者接受氯沙坦钾100mg、苯磺酸氨氯地平5mg模拟剂、氯沙坦钾50mg模拟剂治疗;B3组患者接受苯磺酸氨氯地平5mg、氯沙坦钾50mg模拟剂、氯沙坦钾100mg模拟剂治疗;C1组患者接受苯磺酸氨氯地平5mg、氯沙坦钾50mg、氯沙坦钾100mg模拟剂治疗;C2组患者接受苯磺酸氨氯地平5mg、氯沙坦钾100mg、氯沙坦钾50mg模拟剂治疗。分别在0、4、8周评估坐位舒张压和坐位收缩压及其变化值,并记录不良事件。结果治疗8周后,苯磺酸氨氯地平和氯沙坦钾联合用药组(5/50mg和5/100mg,C1+C2组)的坐位舒张压[(-13.2±9.3)比(-8.3±7.2)mmHg,F=-4.813,P<0.001]和坐位收缩压[(-19.9±15.5)比(-11.9±14.3)mmHg,F=-4.550,P<0.001]的改变值均优于单药组(B1+B2+B3组)。析因分析表明苯磺酸氨氯地平5mg以及氯沙坦钾100mg对于治疗8周后的坐位舒张压和收缩压均有明显影响(均P<0.05)。两种药物间无交互作用(均P>0.1)。各组间不良事件发生率差异无统计学意义(P=0.689)。仅在A组(2.0%)和B3组(2.1%)各有1例重度不良事件发生。结论与单药方案相比,苯磺酸氨氯地平联合氯沙坦钾(5/50mg和5/100mg)方案治疗原发性轻、中度高血压患者有更好的降压效果,不增加不良事件发生率,且两种药物之间无交互作用。Objective To evaluate the efficacy and safety of amlodipine besylate plus losartan potassium and their interaction on the antihypertensive effect in patients with mild to moderate essential hypertension based on the factorial study design.Methods This was an 8-week,randomized,double-blind,factorial design,phaseⅡ,multicenter clinical study.A total of 299patients with mild to moderate essential hypertension were included and were subsequently divided into 6groups in a 1∶1∶1∶1∶1∶1ratio.Patients in group A were treated with amlodipine besylate 5mg simulant,losartan potassium 50mg simulant,and losartan potassium 100mg simulant.Patients in group B1were administrated with losartan potassium 50mg,amlodipine besylate 5mg simulant,and losartan potassium 100mg simulant.Losartan potassium 100mg,amlodipine besylate 5mg simulant,and losartan potassium 50mg simulant were applied in patients in group B2.Patients in group B3were treated with amlodipine besylate 5mg,losartan potassium 50mg simulant,and losartan potassium 100mg simulant.Furthermore,patients in C1group were administrated with amlodipine besylate 5mg,losartan potassium 50mg,and losartan potassium 100mg simulant;meanwhile,the amlodipine besylate 5mg,losartan potassium 100mg,and losartan potassium 50mg simulant were applied in the patients in C2group.Sitting diastolic and systolic blood pressure and their changes were evaluated at 0,4,and 8weeks,respectively.Furthermore,adverse events were recorded.Results After 8weeks of treatment,the changes in sitting diastolic blood pressure[(-13.2±9.3)vs(-8.3±7.2)mmHg,F=-4.813,P<0.001]and sitting systolic blood pressure[(-19.9±15.5)vs(-11.9±14.3)mmHg,F=-4.550,P<0.001]in the combination group(amlodipine besylate plus losartan potassium 5/50mg and 5/100mg,C1+C2 group)were more significant than those in the monotherapy group(B1+B2+B3group).According to the factorial analysis,amlodipine besylate 5mg and losartan potassium 100mg could affect sitting diastolic blood pressure and sitting systolic blood pressure at 8weeks

关 键 词：苯磺酸氨氯地平 氯沙坦钾 高血压 析因分析 疗效 安全性 

分 类 号：R544.1[医药卫生—心血管疾病]