Improving antihypertensive efficacy while maintaining placebo-like tolerability

Abstract

Potency and efficacy, duration of action, organ-specific effects and tolerability are the main considerations when choosing among antihypertensive therapies. Candesartan has been shown in in vitro animal models to bind insurmountably to the angiotensin II type 1 (AT1) receptor, thus providing effective blockade of all the major negative cardiovascular effects of angiotensin II. Its binding characteristics differentiate candesartan from other AT1-receptor blockers. Candesartan cilexetil has been found to produce a predictable and pronounced dose-dependent decrease in blood pressure, with placebo-like tolerability even at the highest doses studied. In comparison with the standard 50-mg dose of losartan, candesartan cilexetil, 16 mg, was significantly more effective in suppressing the renin-angiotensin system and in reducing trough diastolic blood pressure. Pooled results from placebo-controlled trials also indicate that candesartan cilexetil has equivalent efficacy to irbesartan. In addition, the extent of blood pressure lowering by candesartan cilexetil has been shown to be similar to that of agents in the other major classes of antihypertensive drugs, and to be effective in combination therapy with diuretics and calcium channel blockers. Candesartan cilexetil combines 24-h blood pressure lowering with placebo-like tolerability and is therefore an important advance in antihypertensive therapy.