Eplerenone: a selective aldosterone blocker.
Recent studies suggest that aldosterone may play a larger role than once appreciated in normal physiologic function and cardiovascular disease. Some of the adverse cardiovascular effects that have been described include cardiac and vascular fibrosis, vascular necrosis and inflammation, impaired endothelial function, reduced fibrinolysis, hypertension, left ventricular hypertrophy (LVH), congestive heart failure, and cardiac arrhythmias. In light of these findings, the ability to block the actions of aldosterone has gained increased therapeutic importance. Eplerenone is a selective aldosterone receptor blocker that displays little interaction with androgen and progesterone receptors. Eplerenone has already been approved for the treatment of systemic hypertension and has been evaluated in numerous hypertension subgroups, including patients with low plasma renin activity; diabetes; LVH; uncontrolled blood pressure while receiving monotherapy with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta-blockers; and in black patients. Results of these trials indicate that eplerenone lowers blood pressure and reduces end-organ damage. Further proof of the therapeutic importance of mineralocorticoid receptor blockade comes from the eplerenone post acute myocardial infarction survival and efficacy study (EPHESUS). In this large-scale clinical outcome trial, eplerenone was shown to reduce total mortality by 15% as well as the combined endpoint of cardiovascular mortality/cardiovascular hospitalization by 13% when administered at a mean of 7.3 days post myocardial infarction to patients with evidence of systolic left ventricular dysfunction and symptoms of heart failure. Eplerenone is well tolerated, with an adverse effect profile comparable to placebo. The advent of selective aldosterone blockers, such as eplerenone, should prove to be of great therapeutic value in hypertension control and prevention of cardiovascular disease and associated end-organ damage.
Stier
Charles T
CT
Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA. Charles_Stier@nymc.edu.
D000818:Animals; D002986:Clinical Trials as Topic; D000077545:Eplerenone; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000209:etiology; D000451:Mineralocorticoid Receptor Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone