EMPHASIS-HF trial results show eplerenone reduces risk of death and hospitalization by 37% in patients with systolic heart failure.
The results of the Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure (EMPHASIS-HF) trial were announced at the AHA Scientific Sessions 2010 and also published in the NEJM in an article titled “Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms.”
In the EMPHASIS-HF trial, investigators randomly assigned 2737 patients “with New York Heart Association class II heart failure and an ejection fraction of no more than 35% to receive eplerenone (up to 50 mg daily) or placebo, in addition to recommended therapy.” The goal of the trial was to “investigate the effects of eplerenone, added to evidence-based therapy, on clinical outcomes in patients with systolic heart failure and mild symptoms (ie, NYHA functional class II symptoms). Primary outcome of the study was “a composite of death from cardiovascular causes or a first hospitalization for heart failure.”
The study authors reported that death from cardiovascular causes or hospitalization for heart failure occurred in 18% of patients (249 patients) in the eplerenone group, compared to nearly 26% of patients (356 patients) in the placebo group. They reported that 270 patients (19.8%) in the eplerenone group died from any cause or were hospitalized for heart failure, compared to 376 patients (27.4%) in the placebo group. A total of 171 patients (12.5%) in the eplerenone group died, compared to 213 patients (15.5%) in the placebo group died. In the eplerenone group, 408 patients (29.9%) were hospitalized for any reason (including 164 for heart failure), compared to 491 (35.8%) patients in the placebo group (including 253 for ehart failure).
In an editorial accompanying the article in NEJM, Paul Armstrong, MD, notes that this study shows that “eplerenone reduces the rate of death from cardiovascular causes or hospitalization for heart failure by approximately 37%, as compared with placebo, in patients with functional class II heart failure.” However, Armstrong also notes that several characteristics of this patient cohort invite closer review, pointing out that a large portion of these patients had a prior episode of hospitalization for heart failure and a history of myocardial infarction; hypertension, atrial fibrillation, and/or diabetes. The relatively large percentage of patients with left bundle-branch block and a mean QRS duration of 122 msec also mark this group as high-risk. The fact that, contra current guidelines, the patients in this study had lower than expected rates of the infrequent use of implantable defibrillators or cardiac resynchronization therapy, leading Armstrong to ask “whether eplerenone would have fared as impressively had a larger proportion of the study population received implantable electrical devices.” Still, Armstrong writes that the EMPHASIS-HF results “have added real value to the management of heart failure” and “open doors for investigating aldosterone antagonism in other cardiovascular diseases.”
A news release from the AHA states that under current guidelines, “aldosterone antagonists, including eplerenone and the older spironolactone, are recommended only for patients with moderate to severe heart failure and reduced heart function or for patients with heart failure following a recent heart attack” Now, according to lead author Faiez Zannad, MD, PhD, professor of therapeutics and director of the Clinical Investigation Center at the Nancy University Hospital Center in Nancy, France, “This treatment is certainly going to change the guidelines for mild heart failure. Now patients with all kinds of severity of systolic heart failure, whether it is post-myocardial infarction, with mild or severe symptoms, are potentially eligible for some kind of aldosterone blockade, and, certainly, for eplerenone.”