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: 55.87). 11/2010; 364(1):11-21. DOI: 10.1056/NEJMoa1009492
Source: PubMed


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; number, NCT00232180.).

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    • "Clinical trials conducted by the Randomized Aldactone Evaluation Study (5) and Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (6) have demonstrated that the receptor antagonists of aldosterone may significantly reduce cardiovascular-associated mortality in patients with severe heart failure. Recent studies have also shown that the receptor antagonists of mineralocorticoids may improve the survival of patients with systolic heart failure or mild to severe symptoms of heart failure (7–9). Clinical data have indicated that angiotensin-converting enzyme inhibitors are an effective therapeutic strategy for the treatment of heart failure to inhibit aldosterone and improve cardiac remodeling. "
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    ABSTRACT: The aim of the present study was to investigate the effects of spironolactone and losartan on the early healing stage of acute myocardial infarction (AMI) in rats. An AMI rat model was established and the rats were randomly divided into four groups: AMI (n=12), AMI + spironolactone (AMI + S; n=12), AMI + losartan (AMI + L; n=12) and AMI + spironolactone combined with losartan (AMI + S + L; n=12). Sham-operated rats served as a control group (n=12). The expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the non-infarcted myocardium surrounding the AMI area were determined using immunohistochemistry. In addition, the capillary density in the non-infarcted myocardium surrounding the AMI area was detected. The capillary densities around the infarcted area in the AMI and treatment groups at day 7 and 14 following AMI surgery were significantly higher compared with the sham-operated rats. Compared with the AMI group, the capillary densities around the infarcted area and the ratio of MMPs/TIMP-1 were increased in the treatment groups following AMI surgery; however, the increased ratio of MMPs/TIMP-1 was reduced at day 14 following AMI surgery. Therefore, these results indicated that spironolactone and losartan may promote the formation of collateral circulation in the non-infarcted tissue surrounding the infarcted area by regulating the production of MMPs.
    Experimental and therapeutic medicine 09/2014; 8(3):978-982. DOI:10.3892/etm.2014.1791 · 1.27 Impact Factor
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    • "Despite that, addition of potassium supplements or potassium-sparing diuretics, including aldosterone receptor blockers (such as spironolactone and eplerenone) or epithelial sodium channel blockers (such as amiloride and triamterene) can sometimes be necessary, depending on the clinical characteristics of the patient.94 Combination with an aldosterone receptor blocker may be particularly beneficial in hypertensive patients with heart failure.95–97 "
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    ABSTRACT: Combined therapy is required in the majority of patients with hypertension to achieve blood pressure (BP) targets. Although different antihypertensive drugs can be combined, not all combinations are equally effective and safe. In this context, the combination of a renin angiotensin system inhibitor with a diuretic, usually a thiazide, particularly hydrochlorothiazide (HCTZ) or thiazide-like diuretics, such as chlorthalidone or indapamide, is recommended. However, not all diuretics are equal. Although HCTZ, chlorthalidone, and indapamide as add-on therapy effectively reduce BP levels, the majority of studies have obtained greater BP reductions with chlorthalidone or indapamide than with HCTZ. Moreover, there are data showing benefits with chlorthalidone or indapamide beyond BP. Thus, chlorthalidone seems to have pleiotropic effects beyond BP reduction. Moreover, compared with placebo, chlorthalidone has small effects on fasting glucose and total cholesterol, and compared with HCTZ, chlorthalidone achieves significantly lower total cholesterol and low-density lipoprotein cholesterol levels. Similarly, indapamide has demonstrated no negative impact on glucose or lipid metabolism. More importantly, although head-to-head clinical trials comparing the effects of indapamide or chlorthalidone with HCTZ are not available, indirect comparisons and post hoc analyses suggest that the use of chlorthalidone or indapamide is associated with a reduction in cardiovascular events. Despite this, the most frequent diuretic used in clinical practice as add-on therapy for hypertension is HCTZ. The purpose of this review is to update the published data on the efficacy and safety of HCTZ, chlorthalidone, and indapamide as add-on therapy in patients with hypertension.
    Integrated Blood Pressure Control 07/2014; 7(1):35-47. DOI:10.2147/IBPC.S40248
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    • "Subsequently, Juurlink et al. reported an increase in the incidence of hyperkalemia and associated morbidity and mortality with the increased use of spironolactone in patients with heart failure [4]. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) trial reported a reduction in the risk of death from cardiovascular causes in patients with New York Heart Association class II heart failure treated with eplerenone, leading to the possibility of a higher incidence of hyperkalemia [9, 10]. "
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    ABSTRACT: Introduction The aim of the study was to investigate predictors of mortality in patients hospitalized with hyperkalemia. Material and methods Data among hospitalized patients with hyperkalemia (serum potassium ≥ 5.1 mEq/l) were collected. Patients with end-stage renal disease on dialysis were excluded. Results Of 15,608 hospitalizations, 451 (2.9%) episodes of hyperkalemia occurred in 408 patients. In patients with hyperkalemia, chronic kidney disease, hypertension, diabetes, coronary artery disease and heart failure were common comorbidities. Acute kidney injury (AKI) and metabolic acidosis were common metabolic abnormalities, and 359 patients (88%) were on at least one drug associated with hyperkalemia. Mean duration to resolution of hyperkalemia was 12 ±9.9 h. Nonsteroidal anti-inflammatory drugs (HR = 1.59), highest potassium level (HR = 0.61), tissue necrosis (HR = 0.61), metabolic acidosis (HR = 0.77), and AKI (HR = 0.77) were significant independent determinants of duration prior to hyperkalemia resolution. Tissue necrosis (OR = 4.55), potassium supplementation (OR = 5.46), metabolic acidosis (OR = 4.84), use of calcium gluconate for treatment of hyperkalemia (OR = 4.62), AKI (OR = 3.89), and prolonged duration of hyperkalemia (OR = 1.06) were significant independent predictors of in-hospital mortality. Conclusions Tissue necrosis, potassium supplementation, metabolic acidosis, calcium gluconate for treatment of hyperkalemia, AKI and prolonged duration of hyperkalemia are independent predictors of in-hospital mortality.
    Archives of Medical Science 05/2014; 10(2):251-7. DOI:10.5114/aoms.2014.42577 · 2.03 Impact Factor
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