Serum Potassium and Clinical Outcomes in the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS)

Abstract

Background— Aldosterone blockade is recommended for patients with congestive heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction; however, the perceived risk of hyperkalemia may limit implementation of this therapeutic approach. This subanalysis examined the relationship between eplerenone, serum potassium (K + ), and clinical outcomes in the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Methods and Results— Hospitalized patients with congestive heart failure after acute myocardial infarction complicated by left ventricular systolic dysfunction (left ventricular ejection fraction ≤40%) treated with standard therapy were randomized 3 to 14 days after the acute myocardial infarction to additional treatment with eplerenone (25 to 50 mg/d; n=3319) or placebo (n=3313). Patients were excluded if baseline K + was >5.0 mEq/L or serum creatinine was >2.5 mg/dL. In patients receiving standard therapy, the addition of eplerenone resulted in a 4.4% absolute increase in the incidence of K + >5.5 mEq/L, a 1.6% increase of K + ≥6.0 mEq/L, and a 4.7% absolute decrease in hypokalemia (K + <3.5 mEq/L). Four independent baseline predictors of hyperkalemia (defined as ≥6.0 mEq/L) were identified: potassium (K + greater than the median; 4.3 mEq/L), estimated glomerular filtration rate (≤60 mL · min −1 · 1.73 m −2 ), history of diabetes mellitus, and prior use of antiarrhythmic agents. None of these independent baseline risk factors significantly impacted the cardiovascular benefit of eplerenone for reducing all-cause mortality. Conclusions— Use of selective aldosterone blockade with eplerenone within the dose range of 25 to 50 mg/d in post–acute myocardial infarction patients with heart failure and left ventricular systolic dysfunction who are treated with standard therapy improves outcomes without an excess of risk of hyperkalemia (≥6.0 mEq/L) when periodic monitoring of serum K + is instituted.