A factorial design to assess the safety and efficacy of olmesartan medoxomil and hydrochlorothiazide combination therapy

Hypertension is a multifactorial disease, with many patients requiring more than one agent for adequate blood pressure (BP) control. Hydrochlorothiazide (HCTZ) has been shown to potentiate the antihypertensive efficacy of angiotensin receptor blockers (ARBs). This study assessed the efficacy and safety of the ARB olmesartan medoxomil in combination with HCTZ. This was a randomized, double-blind, multicenter study. A total of 502 subjects with mild-to-moderate hypertension (seated diastolic BP [SeDBP] 100–115 mm Hg) were randomized to 1 of 12 groups: placebo, monotherapy with olmesartan medoxomil (10, 20, or 40 mg/d) or HCTZ (12.5 or 25 mg/d), or 1 of 6 olmesartan medoxomil/HCTZ combination groups. The primary end point was the change from baseline in mean trough SeDBP at Week 8. There were no significant differences in baseline vitals signs among the 12 treatment groups; mean SeDBP and mean seated systolic BP (SeSBP) ranged from 102.6 to 104.4 mm Hg and 151.9 to 156.6 mm Hg, respectively. At Week 8, olmesartan medoxomil/HCTZ combination therapy demonstrated greater reductions in SeSBP/SeDBP than did monotherapy with either component. All olmesartan medoxomil/HCTZ combinations significantly reduced SeSBP/SeDBP compared with placebo. Changes from baseline in SeSBP/SeDBP for the starting 20 mg/d dose of olmesartan medoxomil, alone and in combination with HCTZ 12.5 or 25 mg/d, were 15.5/13.8, 20.1/16.4, and 27.1/20.0 mm Hg, respectively. Corresponding SeSBP/SeDBP reductions at the 40 mg/d maximum dose of olmesartan medoxomil, alone and in combination with HCTZ 12.5 or 25 mg/d, were 16.0/14.6, 20.6/17.3, and 26.8/21.9 mm Hg, respectively. Reductions in SeSBP/SeDBP with placebo were 3.3/8.2 mm Hg. The overall incidence of AEs in all treatment groups was similar to that of placebo. The combination of olmesartan medoxomil/HCTZ is an effective and well tolerated therapeutic option. The combination produces dose-dependent reductions in SeSBP/SeDBP of up to 27/22 mm Hg, with an overall incidence of AEs similar to that of placebo. This combination should prove useful in a wide variety of hypertensive patients.