THERAPEUTIC BENEFIT OF A LOW-DOSAGE OF IN DAPAMIDE - RESULT OF A DOUBLE-BLIND, PLACEBO-CONTROLLED EUROPEAN STUDY

Indapamide is a diuretic prescribed in the treatment of hypertension a t the dosage of 2.5 mg per day. In accordance with international recom mendations concerning the need to use low doses of antihypertensives, a new lower-dose form of indapamide has been developed to achieve the best safety/efficacy ratio by decreasing the incidence of hypokalemia. A new pharmaceutical sustained-release (SR) form was developed to giv e a smooth pharmacokinetic profile in comparison with the indapamide i nstant release (IR) form. The aim of this study was to determine the l owest new dosage of the SR form producing similar hypertensive efficac y as the LR form, and decreasing the percentage of patients with a ser um potassium concentration below 3.4 mmol/l. This multicenter study wa s designed as a single-blind, run-in, placebo period of 1 month, follo wed by a double-blind, active treatment period of 2 months, using para llel groups : 285 patients with essential uncomplicated mild-to-modera te hypertension (95 mmHg less than or equal to supine diastolic blood pressure (sDBP) less than or equal to 114 mmHg) were included and rand omly treated by either IR indapamide (2.5 mg) or SR indapamide (1.5, 2 .0, 2.5 mg). After 2 months of active treatment, the one-way analysis of variance on the principal criterion (difference in sDBP between M2 and MO) revealed a significant treatment effect (p = 0.016). The mean drop in sDBP (+/- standard deviation) was 5.8 mmHg (+/-8.6) after 2 mo nths of placebo; 10.1 mmHg (+/-7.0) after indapamide IR 2.5 mg; and 11 .0 mmHg (+/-9.4), 8.9 mmHg (+/-9.4), and 10.5 mmHg (+/-8.5) after inda pamide SR 1.5 mg, 2 mg, and 2.5 mg, respectively. The difference betwe en the placebo and indapamide treatment was significant (p less than o r equal to 0.05). No significant difference was detected between the v arious indapamide treatments, i.e., no difference between the IR and S R formulations, no difference between the various dosages of the SR fo rm, and therefore no dose/effect relationship in the dose interval tes ted (SR 1.5, 2, and 2.5 mg). The incidence of patients with a serum po tassium concentration less than 3.4 mmol/l was lower with indapamide S R 1.5 mg (11 %) than with indapamide 2.5 mg, SR 2 mg, and SR 2.5 mg, r espectively : 29 %, 18 % and 14 %. These results show the interest of a low dose of indapamide in improving the safety while producing the s ame antihypertensive efficacy.