Elsevier

American Heart Journal

Volume 137, Issue 1, January 1999, Pages 118-125
American Heart Journal

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

https://doi.org/10.1016/S0002-8703(99)70467-9Get rights and content

Abstract

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 A prequalification washout period (antihypertensive medications withdrawn) and a 2-week qualification period (patients received single-blind placebo) preceded a 10-week, double-blind treatment period.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.)

Section snippets

Study design

This double-blind, randomized, placebo-controlled, parallel-group, dose-titration, outpatient study was conducted at 21 sites in the United States on patients with stage I and stage II essential hypertension. The study was divided into 4 periods. The prequalification period was a 2- to 4-week washout period during which antihypertensive medication was discontinued and placebo was given under single-blind conditions. The next was a qualification period of 2 weeks during which the patients took

Results

Of the 262 patients enrolled in the study, 132 were randomly assigned to receive tasosartan and 130 to receive placebo. Table I shows the demographic characteristics for the tasosartan and placebo groups.

. Clinical characteristics

CharacteristicsTasosartan (n = 132)Placebo (n = 130)
Age (yr)52.2 ± 9.652.5 ± 9.7
Range(23-69)(26-69)
Sex (No. of patients)
Male8892
Female4438
Race (No. of patients)
White105100
Black1823
Hispanic64
Asian22
Other11
Weight (kg)86.0 ± 15.388.3 ± 17
Height (cm)173.0 ± 9.1171.9 ± 11.0

Discussion

Pharmacologic interruption of the renin-angiotensin system has been shown to be extremely useful in the management of hypertension.12, 13, 14 In addition to reducing blood pressure, reduction of angiotensin II activity has been associated with regression of left ventricular hypertrophy,15 improved arterial compliance,16 increased insulin sensitivity,17, 18 and reduction in proteinuria in patients with moderate renal function impairment.19

ACEIs, which until recently have been the only clinically

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    Supported by a grant from Wyeth-Ayerst Research.

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    Reprint requests: Joel M. Neutel, MD, 505 S Main St, Suite 1025, Orange, CA 92868.

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