A randomized, double-blind, forced-titration study to compare olmesartan medoxomil versus losartan potassium in patients with stage 1 and 2 hypertension.

Objective: To evaluate the comparative efficacy and safety of once-daily olmesartan medoxomil (OM) and losartan potassium (LOS) in patients with hypertension.

Methods: This was a multicenter, prospective, randomized, double-blind, active-comparator, forced-titration study. After a 3-week placebo run-in, 941 patients were randomized in an 8:1:9 ratio to once-daily treatment with OM (20 mg for 4 weeks, then OM 40 mg for 4 weeks [n = 420]), placebo plus OM (placebo for 2 weeks, then OM 20 mg for 2 weeks and OM 40 mg for 4 weeks [n = 52]), or LOS (50 mg for 4 weeks, then LOS 100 mg for 4 weeks [n = 469]). A subset of 246 patients underwent ambulatory blood pressure (BP) monitoring. The primary endpoint was mean change from baseline in trough seated cuff diastolic BP (SeDBP) at week 8. Secondary endpoints were mean changes from baseline in trough SeDBP at week 4 and seated systolic BP (SeSBP) at weeks 4 and 8. Tertiary endpoints included change from baseline in mean 24-hour ambulatory BP at weeks 4 and 8 and percentage of patients achieving seated cuff BP (SeBP) goal of < 140/90 mm Hg and mean 24-hour ambulatory BP target of < 130/80 mm Hg at weeks 4 and 8.

Results: At week 8, least-squares (LS) mean (± standard error) SeDBP reductions from baseline were 9.7 ± 0.5 and 7.1 ± 0.5 mm Hg (treatment difference: -2.5 ± 0.6 mm Hg; P < 0.0001) and LS mean SeSBP reductions were 13.6 ± 0.7 and 9.7 ± 0.7 mm Hg (treatment difference: -3.9 ± 1.0 mm Hg; P = 0.0001) for OM versus LOS, respectively. A significantly greater proportion of patients receiving OM reached SeBP goal of < 140/90 mm Hg at week 8. There was a similar incidence of adverse events with OM and LOS.

Conclusion: Treatment with low- and high-dose OM achieved superior SeBP reductions compared with low- and high-dose LOS, resulting in significantly more patients achieving SeBP goal, with similar tolerability.