**6.2.1 Essential hypertension**

Eplerenone has been repeatedly tested in patients with mild to moderate essential hypertension. One uncontrolled open-label study and many randomized controlled trials have documented the antihypertensive effect of eplerenone when compared to either placebo or other classes of antihypertensive agents. Controlled studies have compared the blood pressure lowering effects of eplerenone at doses comprised form 50 to 400 mg/day with those of either placebo, enalapril, losartan, amlodipine, or spironolactone. In these studies, follow-up duration was from 2 to 14 months. In all studies, eplerenone was more effective than placebo in reducing blood pressure, in two studies it was more potent than losartan, and in the remaining studies the hypotensive effects were comparable to those of enalapril, amlodipine, and spironolactone. Similar to spironolactone, none of these studies reported results for hard cardiovascular endpoints including mortality and major cardiovascular events and therefore there is no evidence that eplerenone improves cardiovascular outcomes in hypertensive patients.

Eplerenone has been demonstrated to be beneficial also on hypertension-related subclinical organ damage. In the 4-E Left Ventricular Hypertrophy Study, regression of left ventricular hypertrophy was compared in essential hypertensive patients who were treated with eplerenone, enalapril, or their combination for 9 months. Left ventricular mass index decreased significantly and comparably in patients treated with eplerenone or enalapril, whereas the combination of the two agents showed additive effects on left ventricular mass reduction. In other studies, eplerenone was reported to be more effective than amlodipine, enalapril, or losartan in decreasing urinary albumin excretion.

Despite eplerenone has a satisfactory tolerability and safety profile even at the highest doses that have been clinically tested (200 mg/day), its effects on blood pressure in essential hypertension and primary aldosteronism are inferior to those of spironolactone.
