The aldosterone antagonist and facultative diuretic eplerenone: a critical review

Eplerenone is a new aldosterone-receptor blocker that differs from spironolactone by virtue of higher selectivity for the aldosterone receptor. Therefore, eplerenone treatment is associated with comparative and absolute low incidences of gynecomastia, mastodynia, and abnormal vaginal bleeding. Similarly, a lower incidence of sexual impotence than that associated with spironolactone administration may be anticipated. Eplerenone and spironolactone increase natriuresis and cause renal retention of potassium when plasma aldosterone is high, i.e., both agents are facultative diuretics. Eplerenone reduces high blood pressure effectively. The results of a recent large study and an ensuing meta-analysis on antihypertensive treatment suggest that a diuretic should be the first-choice agent in most circumstances. Low-dose eplerenone combinations with a low-dose thiazide-type diuretic appear to be options worth investigating, since the overall cardiovascular benefit brought about by reducing blood pressure with the thiazide would be increased, inter alia, by the antikaliuretic action and by the blockade of extrarenal aldosterone receptors provoked by eplerenone. Eplerenone should replace spironolactone as a natriuretic and antikaliuretic in heart failure and as add-on treatment in severe systolic cardiac insufficiency, and it is indicated after an acute myocardial infarction complicated by left ventricular dysfunction and heart failure. The finding that hypertension control with diuretic-based pharmacotherapy results in better prevention of heart failure than pressure reduction with other drugs makes it pertinent to investigate whether diuretics in general, and eplerenone in particular, should constitute part of the initial pharmacotherapy for heart failure when there is no overt fluid retention and independent of the etiology. Eplerenone may cause hyperkalemia, and it might favor the development of metabolic acidosis or hyponatraemia in some circumstances.