Efficacy and safety of olmesartan medoxomil and hydrochlorothiazide compared with benazepril and amlodipine besylate.

BACKGROUND: Most patients with stage 2 hypertension require two or more antihypertensive agents in order to achieve the BP goals recommended in current treatment guidelines. Accordingly, combinations of two drugs with different mechanisms of antihypertensive action are widely used.

OBJECTIVE: The aim of this randomized, double-blind, multicenter 12-week study was to compare the efficacy, safety, and tolerability of a combination of olmesartan medoxomil/hydrochlorothiazide (HCTZ) with that of benazepril plus amlodipine besylate in patients with stage 2 hypertension.

METHODS: Patients were eligible for randomization following a 3- to 4-week placebo run-in period if they had either (i) mean seated DBP>or=90 mm Hg but<115 mm Hg and mean seated SBP>or=160 mm Hg but <200 mm Hg, or (ii) mean seated DBP>or=100 mm Hg but<115 mm Hg. The difference in mean seated SBP measured on two separate visits during the run-in period was required to be<or=15 mm Hg. In addition, a mean 8-hour daytime ambulatory DBP>or=95 mm Hg and<115 mm Hg or SBP>145 mm Hg and<or=190 mm Hg were required. Eligible patients were randomized 1:1 to treatment with olmesartan medoxomil (20 mg/day for 2 weeks; then 40 mg/day for 2 weeks; then olmesartan medoxomil/HCTZ 40/12.5 mg/day for 4 weeks; then olmesartan medoxomil/HCTZ 40/25 mg/day for 4 weeks) or benazepril (10 mg/day for 2 weeks; then 20 mg/day for 2 weeks; then benazepril 20 mg/day plus amlodipine besylate 5 mg/day for 4 weeks; then benazepril 20 mg/day plus amlodipine besylate 10 mg/day for 4 weeks). The primary endpoint was change from baseline in mean SBP at the end of week 12 (end of study). Secondary endpoints included DBP after completion of monotherapy and combination therapy at the end of weeks 4 and 12, SBP at the end of week 4, and percentage of patients attaining BP goals of<140/90 mm Hg, <130/85 mm Hg, and<130/80 mm Hg at the end of weeks 4 and 12.

RESULTS: One-hundred and ninety patients were randomized and received at least one dose of study medication. The primary efficacy endpoint of change in mean seated SBP at week 12 was significantly greater with olmesartan medoxomil/HCTZ than with benazepril plus amlodipine besylate (least square [LS] mean change: -32.5 vs -26.5 mm Hg, p=0.024; LS mean treatment difference -6.0 mm Hg; 95% CI -11.1, -0.8 mm Hg). The LS mean change for reduction in DBP approached statistical significance with olmesartan medoxomil/HCTZ compared with the benazepril-based regimen (p=0.056) at week 12 (end of study). BP reductions showed statistically significant differences between treatment groups favoring olmesartan medoxomil/HCTZ in both SBP and DBP at week 8. The percentage of patients achieving goal rates at the end of the study for olmesartan medoxomil/HCTZ and benazepril plus amlodipine besylate, respectively, were 66.3% versus 44.7% (p=0.006) for<140/90 mm Hg, 44.9% versus 21.2% (p=0.001) for<130/85 mm Hg, and 32.6% versus 14.1% (p=0.006) for<130/80 mm Hg. Both treatments were well tolerated.

CONCLUSIONS: Olmesartan medoxomil/HCTZ 40/12.5 and 40/25 mg/day combination therapy was well tolerated and demonstrated a greater antihypertensive effect than benazepril plus amlodipine besylate 20/5 and 20/10 mg/day and this enabled more patients to achieve targeted BP goals.