The role of mineralocorticoid receptor antagonists in the treatment of cardiac failure.
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.
Funder
John W
JW
Prince Henry's Institute of Medical Research, PO Box 5152, Clayton 3168, Victoria, Australia. John.Funder@phimr.monash.edu.au
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D002986:Clinical Trials as Topic; D000077545:Eplerenone; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D006854:Hydrocortisone / Q000502:physiology; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid / Q000187:drug effects; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000077545:Eplerenone; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone