Eplerenone: a selective aldosterone receptor antagonist for patients with heart failure.
OBJECTIVE
To evaluate the pharmacology, pharmacokinetics, safety, and clinical use of eplerenone in heart failure (HF).


METHODS
English-language MEDLINE searches were performed from 1966 to May 2004. Key words included eplerenone, aldosterone receptor antagonist, heart failure, myocardial infarction, left-ventricular dysfunction, and cost-effectiveness. Additional references were identified from bibliographies of selected articles.


METHODS
Human trials evaluating the efficacy, safety, and cost-effectiveness of aldosterone receptor antagonists in HF were evaluated.


RESULTS
Eplerenone is the first selective aldosterone receptor antagonist. The drug is indicated to improve the survival of stable patients with left-ventricular systolic dysfunction (ejection fraction <40%) and clinical evidence of HF following acute myocardial infarction. Efficacy and safety in this population have been demonstrated in a large, randomized clinical trial. Eplerenone is associated with severe and sometimes life-threatening hyperkalemia. Patients with reduced renal function and diabetes, as well as those on other drugs that increase potassium levels, are at highest risk. Eplerenone is metabolized by the cytochrome P450 system and may interact with drugs that interfere with this system. A major advantage of eplerenone over the nonselective aldosterone receptor antagonist spironolactone is lack of binding to progesterone and androgen receptors, which is associated with drug-induced gynecomastia, breast pain, and impotence.


CONCLUSIONS
The addition of eplerenone to traditional HF therapy has been shown to reduce morbidity and mortality in patients who develop left-ventricular dysfunction after acute myocardial infarction. Eplerenone's selectivity reduces sex hormone-related adverse effects. Despite these benefits, the overall cost-effectiveness has yet to be determined.
Barnes
Brian J
BJ
Department of Pharmacy Practice, University of Kansas Medical Center, Kansas City, KS 6610-7231, USA. bbarnes@kumc.edu
Howard
Patricia A
PA
D000818:Animals; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077545:Eplerenone; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015394:Molecular Structure; D016032:Randomized Controlled Trials as Topic; D013148:Spironolactone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*
D002317:Cardiovascular Agents; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone