Eplerenone: hypertension, heart failure and the importance of mineralocorticoid receptor blockade.

Recent interest in mineralocorticoid receptor (MR) antagonism in cardiovascular disease reflects recognition that blockade of the renin-angiotensin system may be followed by a breakthrough in aldosterone levels to or above the normal range. The Randomized Aldactone Evaluation Study (RALES) trial in progressive heart failure, Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) in post-infarct heart failure, and the 4E trial in essential hypertension demonstrated the efficacy of MR blockade in addition to standard therapy. In all three trials, plasma aldosterone levels were low and sodium status unremarkable; this finding, and those of various preclinical studies, point squarely at pathophysiological MR activation by ligands other than aldosterone, most likely normal levels of cortisol, and provide clear evidence for the therapeutic utility of MR blockade in conditions of tissue and organ damage with normal aldosterone levels.