In the Original Article, “Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms,” by Zannad et al., 2737 patients with heart failure and LV systolic dysfunction were given eplerenone or placebo in addition to recommended therapy. Eplerenone significantly reduced the risk of the primary outcome, a composite of death or hospitalization.
In the placebo-controlled Randomized Aldactone Evaluation Study (RALES), adding the mineralocorticoid-receptor antagonist spironolactone to recommended therapy in patients with systolic heart failure and moderate-to-severe symptoms (i.e., New York Heart Association [NYHA] functional class III or IV symptoms) decreased the rate of death from any cause and the risk of hospitalization for cardiovascular reasons.
• What was the aim of this study?
The aim of this study was to investigate the effects of eplerenone, added to evidence-based therapy, on clinical outcomes in patients with systolic heart failure and mild symptoms (i.e., NYHA functional class II symptoms).
• What is the mechanism of action of eplerenone?
Eplerenone is a selective mineralocorticoid-receptor antagonist.
Table 2. Primary Outcome, Component Events, and Key Secondary Outcomes.
Morning Report Questions
Q: Why was this trial stopped prematurely?
A: The trial was stopped prematurely for efficacy, according to prespecified rules, after a median follow-up period of 21 months. The primary outcome occurred in 18.3% of patients in the eplerenone group as compared with 25.9% in the placebo group (hazard ratio, 0.63; 95% confidence interval [CI], 0.54 to 0.74; P<0.001). A total of 12.5% of patients receiving eplerenone and 15.5% of those receiving placebo died (hazard ratio, 0.76; 95% CI, 0.62 to 0.93; P=0.008); 10.8% and 13.5%, respectively, died of cardiovascular causes (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Hospitalizations for heart failure and for any cause were also reduced with eplerenone.
Q: What adverse effect complicated treatment with eplerenone?
A: A serum potassium level above 5.5 mmol per liter was reported in 158 patients (11.8%) in the eplerenone group and 96 patients (7.2%) in the placebo group (P<0.001). Hypokalemia was significantly less common in the eplerenone- as compared to the placebo-treated group.