ACE and heart failure: Consistently, two large clinical trials, Randomized Aldactone Evaluation Study (RALES) [66] and Eplerenone (a highly selective MR antagonist) Postacute myocardial infarction Heart and Survival Study (EPHESUS) [67], have shown that MR antagonism, in addition to standard therapy to control hypertension (i.e., angiotensin converting enzyme inhibitors), substantially reduces morbidity and mortality in patients with severe heart failure or with acute myocardial infarction complicated by left ventricular dysfunction and heart failure, respectively.