Tolerability of a modern antihypertensive agent: candesartan cilexetil

Tolerability and not efficacy is the limiting factor for long-term successful antihypertensive treatment. Since the discontinuation rate of first line antihypertensives may be as high as 50-60% over six months, it is important to develop new agents with an improved efficacy/tolerability ratio. Candesartan cilexetil is particularly promising in this respect. Candesartan is a potent and selective angiotensin II type 1 (AT1) receptor blocker that binds selectively and tightly (insumontable binding) to the receptor. Candesartan is not associated with any increased risk of cough or angiodema. It is an orally effective vasodilator that does not cause reflex tachycardia or first dose hypotension or orthostatic hypotension. In the dose range from 4-16 mg, once daily candesartan cilexetil is not associated with any dose-dependent adverse events and it is equally well tolerated in men and women and by older (> 65 years) and younger (< 65 years) patients. Furthermore, the drug has no adverse effect on glucose homeostasis or plasma lipid profile. In a double-blind comparison with losartan 50 mg od, candesartan cilexetil 16 mg once daily was significantly more effective in lowering the diastolic blood pressure at the end of the 24 h dose interval but was equally well tolerated. In meta-analyses of clinical trials, candesartan cilexetil showed a tolerability profile comparable to that of placebo therapy.