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5 mg模拟剂、氯沙坦钾50 mg模拟剂和氯沙坦钾100 mg模拟剂治疗;B1组患者接受氯沙坦钾50 mg、苯磺酸氨氯地平5 mg模拟剂、氯沙坦钾100 mg模拟剂;B2组患者接受氯沙坦钾100 mg、苯磺酸氨氯地平5 mg模拟剂、氯沙坦钾50 mg模拟剂治疗;B3组患者接受苯磺酸氨氯地平5 mg、氯沙坦钾50 mg模拟剂、氯沙坦钾100 mg模拟剂治疗;C1组患者接受苯磺酸氨氯地平5 mg、氯沙坦钾50 mg、氯沙坦钾100 mg模拟剂治疗;C2组患者接受苯磺酸氨氯地平5 mg、氯沙坦钾100 mg、氯沙坦钾50 mg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(5/50 mg 和 5/100 mg,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5 mg以及氯沙坦钾100 mg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(5/50 mg和5/100 mg)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.
Abstract
Objective To evaluate the efficacy and safety of amlodipine besylate plus losartan potassium and their in-teraction 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,phase Ⅱ,multicenter clinical study.A total of 299 patients with mild to moderate essential hypertension were included and were subse-quently divided into 6 groups ina1∶1∶1∶1∶1∶1 ratio.Patients in group A were treated with amlodipine besy-late 5 mg simulant,losartan potassium 50 mg simulant,and losartan potassium 100 mg simulant.Patients in group B1 were administrated with losartan potassium 50 mg,amlodipine besylate 5 mg simulant,and losartan potassium 100 mg simulant.Losartan potassium 100 mg,amlodipine besylate 5 mg simulant,and losartan potassium 50 mg simulant were applied in patients in group B2.Patients in group B3 were treated with amlodipine besylate 5 mg,losartan potassium 50 mg simulant,and losartan potassium 100 mg simulant.Furthermore,patients in C1 group were administrated with amlodipine besylate 5 mg,losartan potassium 50 mg,and losartan potassium 100 mg simu-lant;meanwhile,the amlodipine besylate 5 mg,losartan potassium 100 mg,and losartan potassium 50 mg simulant were applied in the patients in C2 group.Sitting diastolic and systolic blood pressure and their changes were evalua-ted at 0,4,and 8 weeks,respectively.Furthermore,adverse events were recorded.Results After 8 weeks 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 5/50 mg and 5/100 mg,C1+C2 group)were more significant than those in the monotherapy group(B1+B2+B3 group).According to the factorial analysis,amlodipine besylate 5 mg and losartan potassium 100 mg could affect sitting diastolic blood pressure and sitting systolic blood pressure at 8 weeks after treatment(all P＜0.05).There was no interaction between these two drugs(both P＞0.1).There was no difference in the incidence of adverse events among all groups(P=0.689).Only one severe adverse event occurred in groups A(2.0％)and B3(2.1％)respectively.Conclusions The com-bination of amlodipine besylate and losartan potassium(5/50 mg and 5/100 mg)shows a better antihypertensive effect and does not increase the incidence of adverse events in patients with mild to moderate essential hypertension compared with the single drug regimen.Besides,no interaction effect is observed between them.
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