培哚普利3.5毫克/氨氯地平2.5毫克新型固定剂量复方制剂作为高血压初始治疗的随机评估

Randomized evaluation of a novel, fixed-dose combination of perindopril 3.5 mg/amlodipine 2.5 mg as a first-step treatment in hypertension.

作者信息

Laurent Stéphane, Parati Gianfranco, Chazova Irina, Sirenko Yuriy, Erglis Andrejs, Laucevicius Aleksandras, Farsang Csaba

机构信息

aDepartment of Pharmacology, European Georges Pompidou Hospital and University Paris Descartes, Paris, France bDept of Health Sciences, University of Milano-Bicocca, Milan cDept of Cardiovascular, Neural and Metabolisc Sciences, S. Luca Hospital, Istituto Auxologico Italiano, Milan, Italy dMinistry of Health of Russian Federation / Cardiology Research Complex, Moscow, Russia eNational Scientific Centre, "M.D. Strazhesko Institute of Cardiology" National Academy of Medical Science, Kiev, Ukraine fPauls Stradins Clinical University Hospital, Riga, Latvia gVilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania hSemmelweis University, Budapest, Hungary.

出版信息

J Hypertens. 2015 Mar;33(3):653-61; discussion 662. doi: 10.1097/HJH.0000000000000440.

DOI:10.1097/HJH.0000000000000440

PMID:25479022

Abstract

OBJECTIVE

To evaluate perindopril 3.5 mg/amlodipine 2.5 mg once daily, a novel fixed-dose combination adapted for first-step treatment in patients with hypertension. This fixed dose had to be equivalent to amlodipine 5 mg in terms of blood pressure efficacy, but with an expected better tolerability profile. We selected two drugs with complementary modes of action, with doses chosen so that each drug would contribute similarly to the overall blood pressure-lowering effect

METHODS

: An international, randomized, double-blind, placebo-controlled study with six equal parallel treatment arms and an 8-week randomized treatment period, whose design, clinical significance and non-inferiority criteria were in accordance with European guidelines.

RESULTS

In all, 1581 patients with mild-to-moderate uncomplicated hypertension (mean age 51.7 years) were randomized and 94.7% completed the study. The combination was statistically and clinically superior to placebo (between-group differences: SBP: -7.22 mmHg, DBP: -4.12 mmHg, P < 0.001 for both). Rates of response and normalization of blood pressure were greater with the combination (P < 0.001 for both) and numerical differences relative to placebo were apparent at 2 weeks. The combination was superior to either component given singly (P < 0.001 for both drugs, for SBP and DBP), and was non-inferior to both component drugs given singly at their lowest clinically-approved doses. The components of the combination had similar effects on SBP (perindopril 3.5 mg: -16.3 mmHg; amlodipine 2.5 mg: -16.0 mmHg). Adverse events relating to peripheral oedema were less frequent with the combination than with amlodipine 5 mg.

CONCLUSIONS

The observed blood pressure-lowering efficacy, rapidity of onset of effect and favourable safety profile of the combination perindopril 3.5 mg/amlodipine 2.5 mg indicate its potential suitability for use as first-step treatment in hypertension.

摘要

目的

评估培哚普利3.5毫克/氨氯地平2.5毫克每日一次，这是一种适用于高血压患者初始治疗的新型固定剂量复方制剂。该固定剂量在降压疗效方面必须等同于5毫克氨氯地平，但预期耐受性更好。我们选择了两种具有互补作用模式的药物，并选择了相应剂量，以使每种药物对总体降压效果的贡献相似。

方法

一项国际、随机、双盲、安慰剂对照研究，设有六个相等的平行治疗组，随机治疗期为8周，其设计、临床意义和非劣效性标准符合欧洲指南。

结果

共有1581例轻度至中度单纯性高血压患者（平均年龄51.7岁）被随机分组，94.7%完成了研究。该复方制剂在统计学和临床上均优于安慰剂（组间差异：收缩压：-7.22毫米汞柱，舒张压：-4.12毫米汞柱，两者P均<0.001）。该复方制剂的血压反应率和血压正常化率更高（两者P均<0.001），与安慰剂相比，在2周时就出现了明显的数值差异。该复方制剂优于单独使用的任何一种成分（两种药物的收缩压和舒张压P均<0.001），并且不劣于单独使用的两种成分药物的最低临床批准剂量。该复方制剂的成分对收缩压的影响相似（培哚普利3.5毫克：-16.3毫米汞柱；氨氯地平2.5毫克：-16.0毫米汞柱）。与外周水肿相关的不良事件在该复方制剂组比在5毫克氨氯地平组更少。