Efficacy and tolerability of tasosartan, a novel angiotensin II receptor blocker: Results from a 10-week, double-blind, placebo-controlled, dose-titration study

Background Angiotensin II receptor antagonists are selective blockers of the renin-angiotensin system and represent an alternative to angiotensin-converting enzyme inhibitors in the treatment of hypertension. Tasosartan is a newly developed nonpeptide AT1 receptor blocker. Methods and Results In this double-blind, randomized, dose-titration, multicenter trial, tasosartan and placebo were compared in patients with stage I and stage II hypertension. A prequalification washout period (antihypertensive medications withdrawn) and a 2-week qualification period (patients received single-blind placebo) preceded a 10-week, double-blind treatment period. The patients received either 50 mg tasosartan (n = 132) or placebo (n = 130) once per day and were evaluated once per week. The dose of tasosartan was increased at 3-week intervals to 100 mg and then to 200 mg if the mean sitting diastolic blood pressure (SiDBP) exceeded 90 mm Hg. Compared with placebo, tasosartan produced significantly (P < .05) greater reductions in both SiDBP (–9.4 ± 0.7 vs –2.0 ± 0.7 mm Hg) and sitting systolic blood pressure (SBP) (–12.2 ± 1.2 vs +0.4 ± 1.2 mm Hg). The rate of response (SiDBP ≤90 mm Hg or a decrease from baseline of ≥10 mm Hg) was significantly (P < .05) greater in the tasosartan group than in the placebo group (55% vs 19%). The mean 24-hour blood pressure reduction with tasosartan was –12.6 ± 0.9/–8.1 ± 0.6, significantly greater (P < .05) than the reduction with placebo (+0.6 ± 0.9/+0.5 ± 0.6 mm Hg). The trough-to-peak ratio (determined from the ambulatory data) was 0.66 for DBP and 0.72 for SBP for the tasosartan treatment group, demonstrating 24-hour efficacy with once-a-day administration. The safety profile of tasosartan was similar to placebo. Conclusions These results demonstrate that tasosartan at 50 to 200 mg given once a day over a titration period of 10 weeks was effective and safe in the treatment of essential hypertension. (Am Heart J 1999;137:118-25.)