Article

EMPHASIS Heart Failure Study Group. Eplerenone in patients with systolic heart failure and mild symptoms

INSERM, Centre d'Investigation Clinique 9501 and Unité 961, and the Department of Cardiology, Nancy University, Nancy, France.
New England Journal of Medicine (Impact Factor: 54.42). 11/2010; 364(1):11-21. DOI: 10.1056/NEJMoa1009492
Source: PubMed

ABSTRACT Mineralocorticoid antagonists improve survival among patients with chronic, severe systolic heart failure and heart failure after myocardial infarction. We evaluated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms.
In this randomized, double-blind trial, we 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 primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure.
The trial was stopped prematurely, 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. A serum potassium level exceeding 5.5 mmol per liter occurred in 11.8% of patients in the eplerenone group and 7.2% of those in the placebo group (P<0.001).
Eplerenone, as compared with placebo, reduced both the risk of death and the risk of hospitalization among patients with systolic heart failure and mild symptoms. (Funded by Pfizer; ClinicalTrials.gov number, NCT00232180.).

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    • "Mineralocorticoid receptor antagonists have also become a fundamental component of the standard care for many inpatient and ambulatory heart failure patients. They are indicated in mild to severely symptomatic systolic heart failure patients, decrease mortality by 30–37% and also significantly reduce hospitalizations (Pitt et al., 1999; Zannad et al., 2011). Newer agents such as ivabradine and myosin agonists will likely also impact patient care and outcomes (Swedberg et al., 2010; Malik et al., 2011). "
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    Life sciences 12/2013; 95(2). DOI:10.1016/j.lfs.2013.12.011 · 2.30 Impact Factor
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    • "The renin–angiotensin–aldosterone system is activated during heart failure (HF). Mineralocorticoid receptor (MR) antagonists have been shown to decrease morbidity and mortality not only in patients with severe HF [1] and after myocardial infarction [2] but also in patients with HF class II of the NYHA functional class [3]. The mechanism by which this inhibition induces beneficial effects, however, has not yet been completely clarified [4] [5]. "
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    • "Aldosterone, the last component of the renin-angiotensinaldosterone system (RAAS), plays a pivotal role in the pathophysiology of cardiovascular diseases primarily through mineralocorticoid-receptor-(MR-) dependent actions [1]. Large clinical trials of patients with heart failure have shown that MR antagonists improve morbidity and mortality in conjunction with the current standard of care [2] [3] [4]. However , the circulating plasma aldosterone levels were within the physiological range in these large trials, thus suggesting the critical role of local cardiac RAAS activation in the pathogenesis of heart failure. "
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