Evaluation of the efficacy and tolerability of the combination delapril plus indapamide in the treatment of mild to moderate essential hypertension: a randomised, multicentre, controlled study

Abstract

The aim of the study was to evaluate efficacy and tolerability of two different fixed combinations of an angiotensin-converting enzyme inhibitor and a diuretic: delapril+indapamide (D+I) and captopril+hydrochlor-othiazide (C+H) administered for 6 months to patients with mild to moderate essential hypertension. In all, 96 centres participated in this randomised, parallel groups, controlled study. A total of 829 patients with uncomplicated mild to moderate hypertension were randomised, and 790 were eligible for the analysis of efficacy (intention to treat). Patients of both sexes, aged 18-75 years, newly diagnosed or untreated during the last month were included in the study if their diastolic blood pressure (DBP) was X95 and p114 mmHg. The starting doses of the drugs were delapril 30 mg+indapamide 1.25 mg tablets o.d. or captopril 50 mg+hydrolchlorothia-zide 15 mg tablets o.d. After a 1-month treatment period, nonresponders (DBP 490 mmHg, or decrease in DBP o10 mmHg) had the daily dose increased to either delapril 30 mg+indapamide 2.5 mg or captopril 50 mg+hydrochlorothiazide 25 mg tablets for a further 5 months. The primary assessment of antihypertensive efficacy was the percentage of patients who responded after a 6-month drug treatment. The responder rates were 72.6% with D+I and 62.9% with C+H (P ¼ 0.004 between treatments) after 60 days of treatment, and 92.6% in the D+I and 85.2% in the C+H (Po0.001 between treatments) at the end of the treatment period. The final value of systolic blood pressure was 134.5 7 13.1 mmHg with D+I and 138.3 7 14.0 mmHg with C+H (Po0.001 between treatments). At the final visit, DBP was 84.577.0 mmHg in the D+I group and 85.578.0 mmHg in the control group (P ¼ 0.017 between treatments). In all, 11 patients in the D+I group and 19 patients in the C+H group were withdrawn from the study because of adverse events. In all, 30 patients (7.6%) with D+I and 32 patients (8.1%) with C+H experienced adverse events. In conclusion, D+I was more effective than C+H in terms of overall reduction in blood pressure and response rate. Greater efficacy was obtained without any increase in adverse effects, since both treatments were equally well tolerated.

Efficacy and Tolerability of Delapril Plus Indapamide Versus Lisinopril Plus Hydrochlorothiazide Combination Treatments in Mild to Moderate Hypertension: A Multicenter, Randomized Clinical Study

“…Efficacy analyses [14][15][16][17] demonstrate the capacity of DϩI to significantly reduce SBP and DBP; in particular, the data of this study confirm the normalization rate (82.5%) and responder rate (92.5%) observed in previous controlled trials for DϩI. The results demonstrate a similar antihypertensive efficacy of both combinations and showed similar tolerability between treatments.…”

“…Compared with thiazide diuretics, indapamide appears to have less potassiumdepleting activity, and, in long-term therapy, it induces no negative effect on lipid or glucose metabolism. [9][10][11] Clinical trials [12][13][14][15][16][17] of the combination of delapril plus indapamide (DϩI) showed, both in case of single administration and at steady state, no interaction between the 2 components, and demonstrated its antihypertensive efficacy. The efficacy of this combination therapy in comparative studies 15,16 was significantly higher than that of the single components and was superior to that of captopril plus hydrochlorothiazide.…”

“…[9][10][11] Clinical trials [12][13][14][15][16][17] of the combination of delapril plus indapamide (DϩI) showed, both in case of single administration and at steady state, no interaction between the 2 components, and demonstrated its antihypertensive efficacy. The efficacy of this combination therapy in comparative studies 15,16 was significantly higher than that of the single components and was superior to that of captopril plus hydrochlorothiazide. The DϩI combination was well tolerated, 17 with a low incidence of AEs, which were mainly neurologic (vertigo, headache), respiratory (cough), gastrointestinal, and fatigue.…”

Combination therapy as first-line treatment for hypertension

“…Several such trials have been reported in the past few years [5][6][7][8]. The same mechanism is true for ARB + diuretic combinations [9][10][11][12].…”

“…Much has been written in recent years about the advantages and disadvantages of using fixed drug combinations [5][6][7][8][9][10][11]13,15,[17][18][19][20][21][22][23][24][25][26][27][28][29]. There are also arguments relevant to the proper timing of instituting a chosen fixed combination-that is, as first choice upon initiation of drug therapy or upon reaching the BP goal, after which no further changes are likely to be needed [31][32][33][34][35].…”