• Cardiology Clinical Trials
• Heart Failure

Recent results from the Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure (EMPHASIS-HF) trial showed that eplerenone, compared with placebo, significantly reduced the risk of the composite of cardiovascular (CV) death and hospitalization for heart failure (HF) in patients with chronic systolic NYHA class II HF [NCT00232180; Zannad F et al. N Engl J Med 2011]. Subjects were randomized to eplerenone (up to 50 mg daily) or placebo, in addition to recommended background therapy. Enrollment in the trial, which randomized 2737 patients, was stopped prematurely after a median follow-up of 21 months, when an overwhelming benefit (HR, 0.63; p<0.001) with eplerenone on the primary endpoint of death from CV causes and hospitalization for HF was observed in the secondary interim analysis. After the trial was prematurely stopped for efficacy in May 2010, a subgroup of patients (58% of the patients who were randomized; n=1597) were followed for an additional 10 months on blinded therapy through March 2011, resulting in a mean follow-up of 25 months in the extended follow-up subgroup.

Bertram Pitt, MD, University of Michigan, Ann Arbor, Michigan, USA, presented three sets of new data from the trial: 1) safety and efficacy results of the extended follow-up of the EMPHASIS-HF study; 2) an exploratory analysis of recurrent hospitalization; and 3) analyses in five high-risk subgroups. The five subgroups of individuals who were considered to be at high risk were independently analyzed, including subjects with: age ≥75 years (n=184), left ventricular ejection fraction (LVEF) <30% (n=440), estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m² (n=270), diabetes (n=240), and systolic blood pressure (SBP) <123 mm Hg (n=339).

Consistent with the main study, the primary composite endpoint of CV death or hospitalization for HF was reduced with eplerenone compared with placebo (HR, 0.66; 95% CI, 0.57 to 0.77; p<0.001) in the extended follow-up subgroup. An analysis of the cumulative number of hospitalization for HF (recurrent event analysis) also favored eplerenone (HR, 0.62; 95% CI, 0.53 to 0.72; p<0.001).

There were consistent reductions with eplerenone in the primary endpoint in each of the five individual high-risk groups (Table 1). Additionally, in each of the five subgroups, there were significant reductions with eplerenone in the secondary endpoints of all-cause hospitalization and in hospitalization for HF (p<0.01 for all comparisons).

The safety endpoint of serum potassium greater than 5.5 mmol/L was more frequent with eplerenone overall and among each of the individual high-risk groups (p<0.05 for each comparison). There was no significant increase in serious hyperkalemia (K+ >6.0 mmol/L), hyperkalemia that led to drug discontinuation, hospitalization for hyperkalemia, or hospitalization for worsening renal function for eplerenone patients relative to placebo patients.

These results showed a consistent benefit in the reduction of CV death or hospitalization for HF over continued follow-up and among individual high-risk subgroups. Important reductions were also seen in the secondary endpoints of all-cause hospitalization and in hospitalization for HF. While these results show compelling evidence for efficacy that is consistent with guideline recommendations for this class of medications, there were higher rates of hyperkalemia, and the study protocol required careful monitoring with visits every 4 months. This should be considered when applying these results with eplerenone in clinical practice.

• © 2011 MD Conference Express