In most countries the last two decades have seen a very substantial rise in the prevalence of
heart failure, and in a majority of patients
hypertension is both an antecedent condition and a contributing cause.
Heart failure is also a major cause of hospital admissions; its amelioration and, as far as possible, prevention is therefore important in terms not only of morbidity and premature mortality for the individual patient, but also containment of healthcare costs. Over the past 5 years,
mineralocorticoid receptor (MR) antagonists have been used in two major outcome trials (the Randomized
Aldactone Evaluation Study [
RALES] with
spironolactone, and the
Eplerenone Post-AMI
Heart Failure Efficacy and Survival Study [EPHESUS]), in severe (New York Heart Association class III) and post-
myocardial infarct heart failure, respectively. Experimental studies have largely focused, however, on various animal models of
hypertension; on the basis of a portfolio of clinical studies on the efficacy of
eplerenone, administered either alone and in combination as an
antihypertensive agent, the novel MR antagonist was approved by the FDA for the treatment of
hypertension, though it has yet to be launched. In this review, the two major outcome studies (
RALES, EPHESUS) are discussed in the context of the new biology of
aldosterone action. The relevance to
heart failure of current experimental studies, largely on vascular protection, will also be discussed.