Luccioni R, Sever P S, Di Perri T, Redon J, Laurandin I, Brault Y, Chastang C, Guez D
University Hospital Centre for Timone, Marseille, France.
J Hypertens. 1995 Dec;13(12 Pt 2):1847-51.
The aim of this multicenter, randomly allocated, double-blind, parallel-group study was to evaluate the equivalence of three fixed-dose combination drugs in mild to moderate hypertension: perindopril + indapamide (4 + 1.25 mg), captopril + hydrochlorothiazide (50 + 25 mg) and enalapril + hydrochlorothiazide (20 + 12.5 mg).
After a single-blind, 4-week, placebo run-in phase, 527 patients (mean +/- SD age 54.5 +/- 1.2 years) with a supine diastolic blood pressure of 101.2-101.7 mmHg were randomly assigned to one of the three treatments for 8 weeks. The main evaluation criteria were diastolic blood pressure and serum potassium concentration. Equivalence was assessed on an intention-to-treat basis, using Schuirmann's method, which involves performing two one-tailed statistical tests on the data. Thirty-five patients were withdrawn from the study but there were no differences between groups in the reasons for withdrawal.
Diastolic blood pressure decreased by between 13.1 and 14.2 mmHg in the three groups. The 90% confidence intervals for the differences between perindopril + indapamide and the other treatments were -1.1, +1.7 mmHg for captopril + hydrochlorothiazide and -0.4, +2.6 mmHg for enalapril + hydrochlorothiazide. Schuirmann's test was highly statistically significant (P<0.001 for perindopril + indapamide versus captopril + hydrochlorothiazide; P<0.002 for perindopril + indapamide versus enalapril + hydrochlorothiazide), so that the two one-sided hypotheses that the treatments were not equivalent were rejected at the nominal level of alpha = 0.05. Similarly, the safety of the treatments was equivalent in terms of serum potassium. The 90% confidence intervals of the differences between perindopril + indapamide and the other treatments were -8.7, -1.6% for captopril + hydrochlorothiazide (P = 0.004) and -1.5, +2.7% for enalapril + hydrochlorothiazide (P<0.001).
We conclude that the safety and efficacy of perindopril + indapamide, captopril + hydrochlorothiazide and enalapril + hydrochlorothiazide were equivalent after 8 weeks of treatment in patients with mild to moderate hypertension.
本多中心、随机分配、双盲、平行组研究旨在评估三种固定剂量复方药物治疗轻至中度高血压的等效性：培哚普利+吲达帕胺（4+1.25毫克）、卡托普利+氢氯噻嗪（50+25毫克）和依那普利+氢氯噻嗪（20+12.5毫克）。
在经过单盲、为期4周的安慰剂导入期后，527例仰卧位舒张压为101.2 - 101.7毫米汞柱的患者（平均±标准差年龄54.5±1.2岁）被随机分配至三种治疗方案之一，为期8周。主要评估标准为舒张压和血清钾浓度。基于意向性分析，采用舒尔曼方法评估等效性，该方法涉及对数据进行两次单侧统计检验。35例患者退出研究，但各治疗组间的退出原因无差异。
三组患者的舒张压均下降了13.1至14.2毫米汞柱。培哚普利+吲达帕胺与其他治疗方案差异的90%置信区间，对于卡托普利+氢氯噻嗪为-1.1，+1.7毫米汞柱，对于依那普利+氢氯噻嗪为-0.4，+2.6毫米汞柱。舒尔曼检验具有高度统计学意义（培哚普利+吲达帕胺与卡托普利+氢氯噻嗪相比，P<0.001；培哚普利+吲达帕胺与依那普利+氢氯噻嗪相比，P<0.002），因此在名义显著性水平α = 0.05下，两种治疗方案不等效的单侧假设被拒绝。同样，在血清钾方面，各治疗方案的安全性相当。培哚普利+吲达帕胺与其他治疗方案差异的90%置信区间，对于卡托普利+氢氯噻嗪为-8.7，-1.6%（P = 0.004），对于依那普利+氢氯噻嗪为-1.5，+2.7%（P<0.001）。
我们得出结论，在轻至中度高血压患者中，治疗8周后，培哚普利+吲达帕胺、卡托普利+氢氯噻嗪和依那普利+氢氯噻嗪的安全性和疗效相当。
