DOSE-RELATED ANTIHYPERTENSIVE EFFECTS OF IRBESARTAN IN PATIENTS WITH MILD-TO-MODERATE HYPERTENSION

Two multicenter, double-blind, placebo-controlled, parallel group stud ies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT(1) subtype) a ntagonist irbesartan. The effect of irbesartan withdrawal and the effe ct of adding hydrochlorothiazide (HCTZ) to irbesartan were also assess ed. After a placebo lead-in phase, all patients were randomized to 8 w eeks of double-blind therapy with either placebo (n = 158) or irbesart an at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) o rally once daily. Irbesartan reduced blood pressure in a dose-related manner. Reductions from baseline in trough seated diastolic blood pres sure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg irbesartan. At week 8, statistically significant reductions over pl acebo were observed in trough seated blood pressure with all irbesarta n doses greater than or equal to 50 mg. These reductions reached stati stical significance versus placebo within 2 weeks with 100, 200, and 3 00 mg irbesartan Plasma irbesartan concentrations correlated with dose . Angiotensin II and aldosterone levels generally showed dose-related changes, consistent with AT(1) receptor blockade. In patients not cont rolled at 8 weeks, the addition of 12.5 mg HCTZ resulted in further do se-related reductions in blood pressure. Irbesartan demonstrated a pla cebo-like safety profile and no dose-related toxicity. Irbesartan, adm inistered alone or in combination with HCTZ, was well tolerated. Withd rawal of irbesartan did not result in rebound hypertension or adverse events. Thus, once-daily irbesartan is both an effective and safe anti hypertensive agent for the treatment of mild-to-moderate hypertension. (C) 1998 American Journal of Hypertension, Ltd.