All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor ----------------------------------------------------------- ALDOSTERONE ANTAGONISTS FOR CHF ------------------------------------------------------------- Spironolactone - an ARA (aldosterone receptor antagonist) - is good for CHF but has substantial side effects, including breast swelling and pain in men; reduced sex drive and impotence; and menstrual irregularities in women. A new selective ARA drug (SARA) called eplerenone may give the same benefits without the side effects. Adding spironolactone to ACE inhibitors improves fluid elimination and symptoms. Title: Aldosterone antagonists in hypertension and heart failure. Author: Mantero F, Lucarelli G. Source: Ann Endocrinol (Paris) 2000 Feb;61(1):52-60 PMID: 10790593 ============================================================= It is known that aldosterone worsens CHF by causing edema. Spironolactone blocks aldosterone receptors. The RALES trial showed that spironolactone improved mortality in patients with severe heart failure. Its limitations include unwanted sex hormone side effects. To get the benefits without the side effects, eplerenone is currently being developed by Searle. Eplerenone has excellent selectiveness for the aldosterone receptor over other steroid receptors, eliminating most of the side effects. Title: Mineralocorticoid receptor antagonists: the evolution of utility and pharmacology. Author: Delyani JA. Source: Kidney Int 2000 Apr;57(4):1408-11 PMID: 10760075 ============================================================= Eplerenone is in phase 3 clinical trials. Pharmacia expects to market the drug for CHF in 2002. A world-wide phase 3 survival trial was started in the USA and 30 other countries in January of 2000. The trial studies whether eplerenone reduces mortality in patients who have recently had a heart attack that resulted in heart failure. Title: Eplerenone (GD Searle and Co). Author: Martin J, Krum H. E-mail: J.Martin@alfred.org.au Source: Curr Opin Investig Drugs 2001 Apr;2(4):521-4 PMID: 11566010 ============================================================= Aldosterone is the final product of the RAS : Renin-Angiotensin-Aldosterone systemS). It is a mineral- corticoid hormone that helps maintain electrolyte balance. Although ACE inhibitors and ARBs suppress the RAS, they do not completely control blood levels of aldosterone. Spironolactone does control blood aldosterone levels but due to its uncontrolled binding to other steroid receptors it causes unwelcome side effects. Eplerenone - the first of a new class of drugs called SARAs (Selective Aldosterone Receptor Antagonists) - is being tested. In phase 2 trials, eplerenone controlled blood pressure with once or twice daily dosing, and was safe and well tolerated in CHF patients already taking standard CHF drugs. Ongoing phase 3 trials are underway. Title: Eplerenone: a selective aldosterone receptor antagonist Authors: Delyani JA, Rocha R, Cook CS, Tobert DS, Levin S, Roniker B, Workman DL, Sing Yl, Whelihan B. E-mail: john.a.delyani@pharmacia.com Source: Cardiovasc Drug Rev 2001 Autumn;19(3):185-200 PMID: 11607037 ============================================================= For treating CHF, neurohormonal blockers have been most successful : beta-blockers, ACE inhibitors and ARBs. We now add aldosterone blockers, namely spironolactone. A more recent and more selective aldosterone receptor antagonist is eplerenone. It shows promise in mild to moderate heart failure. The EPHESUS trial randomised 6,200 CHF patients with systolic dysfunction to eplerenone or placebo in addition to standard therapy. The trial will follow patients until 1,012 deaths have occurred (about 2 1/2 years of follow up). Title: Exciting new drugs on the horizon - eplerenone, a selective aldosterone receptor antagonist (SARA). Author: Coats AJ. Source: Int J Cardiol 2001 Aug;80(1):1-4 PMID: 11532539