Eplerenone: a selective aldosterone receptor antagonist for hypertension and heart failure.
Aldosterone has been implicated for many years as an important substance in the pathogenesis of heart disease. Elevated aldosterone concentrations have been documented in patients with hypertension and heart failure, leading to the use of aldosterone antagonists for the treatment of these conditions. Spironolactone has been used for nearly 2 decades for the treatment of hypertension, and more recently, has become a standard agent for the treatment of systolic heart failure. Spironolactone, however, is a nonselective antagonist of the aldosterone receptor, binding also to other steroid receptors and causing a significant percentage of patients to have sex hormone-related adverse effects such as gynecomastia. Eplerenone is the first of a new class of drugs known as selective aldosterone receptor antagonists, which selectively block the aldosterone receptor with minimal effect at other steroid receptors, thereby minimizing many of the hormonal side effects seen with spironolactone. Eplerenone has been shown to be beneficial both as monotherapy and combination therapy for lowering elevated blood pressure in patients with hypertension. The antihypertensive efficacy of eplerenone is roughly similar to that of other antihypertensive agents, although in 1 study black patients responded better with eplerenone than losartan. In addition, eplerenone has demonstrated some renoprotective effects in diabetic patients with hypertension. Recently, eplerenone was shown to significantly reduce mortality and cardiovascular morbidity in post-myocardial infarction patients with systolic heart failure currently taking standard heart failure medications. Eplerenone is generally well tolerated, although hyperkalemia with this agent is of some concern. Eplerenone is metabolized by CYP3A4 and administration with potent inhibitors of this enzyme is contraindicated because of the risk of hyperkalemia. In summary, eplerenone has proven to be beneficial in treating hypertension and post-myocardial infarction heart failure. Its exact place in therapy will in large part be determined by its cost and whether or not future studies will be able to demonstrate a clinical benefit of this agent over spironolactone or other currently available treatments.
D000450:Aldosterone / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D000077545:Eplerenone; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D018161:Receptors, Mineralocorticoid / Q000187:drug effects*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use
D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone