Aldosterone Receptor Antagonists

A 63-year-old woman is evaluated after a recent hospitalization for an acute myocardial infarction. She reports fatigue and exertional dyspnea after ambulating 25 m. Her left ventricular (LV) ejection fraction is 38%, and her medications include aspirin, clopidogrel, a loop diuretic, an angiotensin-converting enzyme inhibitor (ACE-I), and a β-adrenergic receptor antagonist. On physical examination, her blood pressure is 144/92 mm Hg, and her heart rate is 72 bpm. Her jugular venous pressure is 9 cm water, and bilateral inspiratory rales and 1+ peripheral edema are noted. The patient’s serum K+ is 4.5 mEq/L and creatinine is 1.2 mg/dL. She is diagnosed with hypertension and moderate congestive heart failure (CHF) with LV systolic dysfunction. Despite evidence from clinical trials demonstrating a morbidity and mortality advantage for selected patients treated with aldosterone receptor antagonists, these drugs are underused in clinical practice. The Randomized Aldactone Evaluation Study (RALES) and Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) established that spironolactone and eplerenone, respectively, increased survival in patients with severe CHF symptoms from LV systolic dysfunction occurring with minimal exertion or at rest (New York Heart Association [NYHA] class III or IV) or CHF after an acute myocardial infarction.1–3 As a result of these studies, aldosterone receptor antagonists were given an American Heart Association/American College of Cardiology class I recommendation for use, yet only 32% of eligible patients are routinely prescribed these drugs.4,5 This trend likely reflects clinicians’ persisting concerns over reports linking increased community-based spironolactone use with drug-induced deaths and hospitalizations.6 This association is drawn largely from population-based observational data demonstrating a temporal (and not causal) relationship between increased prescription rates of spironolactone and increased rates of hospital admission for the treatment of hyperkalemia and subsequent in-hospital deaths. Given that aldosterone receptor antagonists are often used …