培哚普利／吲哒帕胺复合制剂治疗高血压患者的多中心、随机、双盲对照研究

A randomised,double-blind,multicenter,parallel control clinical study of perindopril /indapamide combination vs. indapamide SR in patients with hypertension

目的:比较低剂量培哚普利／吲哒帕胺复合制剂与吲哒帕胺缓释剂治疗高血压患者血压的变化和治疗反应率及其安全性。方法:共入选原发性高血压病患者231例。经2周安慰剂洗脱期后,分为试验组(n=116)和对照组(n=115)。完成试验患者210例,符合方案分析集(PPS)203例,其中试验组107例,对照组96例。2组随机双盲接受培哚普利2 mg／吲哒帕胺0．625 mg或吲哒帕胺缓释剂(纳催离SR)1．5 mg,qd;治疗6周后,如果舒张压(DBP)<90 mmHg。继续上述治疗;如果DBP≥90 mmHg,试验组改为qid口服培哚普利4 mg／吲哒帕胺1．25 mg;对照组在纳催离SR的基础上加用美托洛尔50 mg,qd,继续治疗6周。部分患者在治疗前及治疗12周时行动态血压检测(ABPM)。结果:用药后第6周时,试验组药物剂量加倍比率为48．6％(52／107),对照组有54．2％(52／96)的病例需加用美托洛尔,两组加药率比较无差异(P=0．43)。与给药前比较,治疗12周后两组DBP均明显下降(P<0．01),下降幅度试验组和对照组平均为12．4和13．6 mmHg(P=0．191),两组收缩压(SBP)在用药后备时点亦均明显下降(P<0．01),下降幅度为15．4和15．7 mmHg。两组ABPM各指标均明显下降,试验组和对照组的DBP谷峰比(T／P)为80％和47％。两组不良事件发生率无差异,主要的不良事件为咳嗽、鼻炎、低钾血症。结论:2种治疗方法12周后均可显著降低DBP和SBP。试验组可以维持24 h平稳降压。两组不良反应发生率相似。

Objective：To evaluate the efficacy and tolerability of perindopril （2 mg） and indapamide （0. 625 mg） compound versus indapamide sustained-released tablets in patients with mild to moderate hypertension. Methods ： A randomized, double blind, muhicenter,parallel control clinical study enrolled 231 patients （aged 18 to 65 years old） with essential hypertension （95 mmHg ≤ sitting DBP 〈 115 mmHg and SBP 〈 180 mmHg）. After the patients experienced a 2-week washed out period, they were randomized to administer either perindopril 2 mg/ indapamide 0.625 mg （n = 116） compound or indapamide SR 1.5 mg alone （n = 115 ） once daily for 6 weeks. At the end of this 6-week course of therapy, patients with sitting DBP 〈 90 mmHg continued the medication regimen, and patients with sitting DBP≥95 mmHg were tapered onto the perindopril 4 mg / indapamide 1.25 mg compound once daily in the bi-therapy group or received an added-on therapy with indapamide SR 1.5 plus metoprolol 50 mg once daily in the mono-therapy group for additional 6 weeks. Patients underwent an ABPM pre-treatment and post the 12-week course of therapy. Results：52 out of the 107 patients （48.6%） tapered the drug regimen up in the bi-therapy group and 52 out of the 96 patients （54.2%） received the adjunctive therapy in the mono-therapy group after the first 6-week course of the therapy; the P value of changing drug regimens in the bi-therapy and the mono-therapy group showed no statistical difference （P = 0.43）. The patients in the bi-therapy and added-on-therapy experienced a reduction of DBP （average down value 12.4 mmHg versus 13.6 mmHg,P = 0. 191 ） and a decrease of SBP （ average down value 15.4 mmHg versus 15.7 mmHg） at the end of the second 6-week course of therapy. The ABPM values showed significant improvements during the treatment in both groups. The mean trough/peak ratio （TPR） of DBP in the bi-therapy and added-on-therapy group was 80% and 47% , respectively. Common adverse events included cough, rhinitis and hypokalaemia. No significant difference was found in the incidence rate of these adverse events in patients with bi-therapy and added-on-therapy. Conclusion： The perindopril and indapamide compound offered an alternative therapy for patients with hypertension.