Irbesartan: a review of its use alone and in combination with hydrochlorothiazideAuthor(s): Claudio Borghi, Sibel Ertek and Arrigo FG Cicero
Blood pressure is one of the most important and frequent risk factors for cardiovascular disease morbidity and mortality; however, it is largely uncontrolled in the population. Inhibition of the renin–angiotensin–aldosterone system provides beneficial effects in the hypertensive population. Association of low-dosed diuretics in drug combinations with renin–angiotensin–aldosterone system-blocking agents allows maximum benefit from potassium depletion and control of the compensatory increase in renin secretion, thus increasing the efficacy and safety of the renin–angiotensin–aldosterone system blockers. Irbesartan is a potent and selective angiotensin II subtype 1 receptor antagonist indicated for use in patients with hypertension, including those with Type 2 diabetes mellitus and nephropathy. Once-daily irbesartan administration provides 24-h control of blood pressure. In patients with mild-to-moderate hypertension, irbesartan was as effective as enalapril, atenolol and amlodipine, and more effective than losartan and valsartan (but not olmesartan), in terms of absolute reduction in blood pressure and response rate. Irbesartan also induced regression of left ventricular hypertrophy. Moreover, irbesartan 300 mg/day exerted a significant renoprotective effect in hypertensive Type 2 diabetics. The relative risk of doubling of serum creatinine was significantly lower with irbesartan than with amlodipine or placebo. It was also found to be effective in nondiabetic nephropaties. Furthermore, irbesartan has peroxisome proliferator-activated receptor agonistic effects in in vitro studies and also demonstrated beneficial effects on inflammatory markers of atherosclerosis and endothelial function. The overall incidence of adverse events is similar to that of placebo. A fixed-dose combination of hydrochlorothiazide and irbesartan show additive antihypertensive effects in a dose-dependent manner up to hydrochlorothiazide 25 mg and irbesartan 300 mg, with high tolerability in diverse patient groups. Effects of combination on end-organ protection must be evaluated by broad-spectrum studies. Ongoing trials with irbesartan and its combination with diuretics may provide necessary data to interpret the value of this association among others.