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TODD R. MARCY, PHARM.D., BCPS, CDE, is Assistant Professor; and TONI L. RIPLEY, PHARM.D., BCPS, is Assistant Professor, University of Oklahoma College of Pharmacy, Oklahoma City.

Address correspondence to Dr. Marcy at the University of Oklahoma College of Pharmacy, P.O. Box 26901, Oklahoma City, OK 73190 (todd-marcy{at}ouhsc.edu).

Purpose. The clinical benefits, adverse effects, pharmacokinetics, and recommendations for the appropriate use of the aldosterone antagonists spironolactone and eplerenone in patients with heart failure are reviewed. Summary. Heart failure is a clinical syndrome characterized by the functional inability of the ventricle to meet the metabolic demands of the body. Renal hypoperfusion occurs as a result of reduced cardiac output, resulting in the activation of the renin–angiotensin–aldosterone system, which compensates for the hypoperfusion. However, this contributes to the pathology of the disease by, among other actions, increasing the release of aldosterone. Aldosterone has been shown to cause coronary inflammation, cardiac hypertrophy, myocardial fibrosis, ventricular arrhythmias, and ischemic and necrotic lesions. There are currently two aldosterone antagonists commercially available in the United States, spironolactone and eplerenone. Spironolactone is a nonselective aldosterone antagonist, and eplerenone is selective to the aldosterone receptor. Although numerous clinical trials have evaluated the efficacy of each drug, no studies have directly compared spironolactone and eplerenone. Both have been shown to improve morbidity and mortality in patients with advanced heart failure. Adverse effects of both spironolactone and eplerenone include potentially life-threatening hyperkalemia, which can be induced by renal insufficiency, diabetes mellitus, advanced heart failure, advanced age, and concurrent drug therapy. Conclusion. Spironolactone and eplerenone are life-saving agents in patients with advanced heart failure and may benefit patients with mild heart failure. Potassium and renal function must be routinely assessed to minimize the risk of life-threatening hyperkalemia. Index terms: Aldosterone antagonists; Diabetes mellitus; Drug interactions; Drug use; Eplerenone; Geriatrics; Heart failure; Kidney failure; Mechanism of action; Mortality; Pharmacokinetics; Rational therapy; Spironolactone; Toxicity