Aldosterone Antagonists in the Treatment of Heart Failure

Todd R. Marcy; Toni L. Ripley


Am J Health Syst Pharm. 2006;63(1):49-58. 

In This Article

Abstract and Introduction

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.

Heart failure is a complex disease affecting about 5 million Americans, with 550,000 new cases diagnosed annually.[1] Although treatment strategies have improved morbidity and mortality rates over the past 20 years, the 5-year mortality rate is approximately 50%.[2,3] Pharmacologic therapy is a major component in the management of heart failure and can include angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), β-blockers, digoxin, diuretics, and aldosterone antagonists. Hydralazine and nitrates continue to be used in some patients with heart failure.

The Randomized Aldactone Evaluation Study (RALES) and the more recently published Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) have established aldosterone antagonists as life-saving additions in the treatment of heart failure.[4,5] However, safety concerns were raised after a recent retrospective evaluation of spironolactone in the Canadian population found a significant increase in the rate of hyperkalemia among heart failure patients receiving aldosterone antagonists.[6]

This review discusses the role of aldosterone antagonists in the treatment of heart failure, including an overview of aldosterone’s role in the pathology of heart failure, the benefits of each aldosterone antagonist, and the adverse events associated with each agent.