Fixed low dose combination therapy in hypertension - a dose response studyof perindopril and indapamide

Objective To establish the optimal dose of the perindopril/indapamide combi nation (Per/Ind) in the treatment of mild or moderate hypertension. Design This was a randomized, double-blind, placebo-controlled, seven-way p arallel-group, dose-ranging study, set in multicenter, outpatient offices/c linics in Europe and Canada. Patients A total of 438 patients aged between 18 and 75 years whose supine diastolic brood pressure was between 95 and 114 mmHg were randomly assigned to an 8-week double-blind treatment with either placebo, Per 2/Ind 0.625, Per 4/Ind 1.25, Per 8/Ind 2.5, Per 0/Ind 1.25, Per 2/Ind 1.25 or Per 8/Ind 1.25 mg. Main outcome measures Systolic and diastolic blood pressure measured in the clinic approximately 24 h after dosing. Results There was a linear dose-response relationship (P < 0.001) for doubl ing the dose of Per 2/Ind 0.625 mg up to Per 8/Ind 2.5 mg with a progressiv e fall in supine diastolic blood pressure (-9.3 to -15.0 mmHg). Combining 1 .25 mg Ind with increasing doses of Per (0, 2, 4 and 8 mg) also showed a li near dose-response relationship (P < 0.001), with supine diastolic blood pr essure falling by -8.0 to -12.0 mmHg compared with a fall of -5.2 mmHg for the placebo group. Similar findings were noted for supine systolic blood pr essure, standing blood pressure and ambulatory blood pressure. Hypokalemia was more common (9.7%) in the Per 8/Ind 2.5 mg group than in the groups rec eiving other doses (0-4.6%). Conclusion The combinations of Per 2/Ind 0.625 mg and Per 4/Ind 1.25 mg wer e effective in reducing blood pressure without producing clinically importa nt side effects. J Hypertens 2000, 18:317-325 (C) Lippincott Williams & Wil kins.