Background-We evaluated the effect of the selective mineralocorticoid receptor antagonist eplerenone on renal function and the interaction between changes in renal function and subsequent cardiovascular outcomes in patients with heart failure and left ventricular systolic dysfunction after an acute myocardial infarction in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Methods and Results-Serial changes in estimated glomerular filtration rate (eGFR) were available in 5792 patients during a 24-month follow-up. Patients assigned to eplerenone had a decline in eGFR with an adjusted mean difference of Ϫ1.4Ϯ0.3 mL ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 compared with placebo (PϽ0.0001), an effect that appeared within the first month (Ϫ1.3Ϯ0.4 mL ⅐ min Ϫ1 ⅐ 1.73 m Ϫ2 ) and persisted throughout the study. Overall, 914 patients experienced a decline in eGFR Ͼ20% in the first month, 16.9% and 14.7% in the eplerenone and placebo groups, respectively (odds ratio, 1.15; 95% confidence interval, 1.02-1.30; Pϭ0.017). In multivariate analyses, determinants of this early decline in eGFR were female sex, age Ն65 years, smoking, left ventricular ejection fraction Ͻ35%, and use of eplerenone and loop diuretic. An early decline in eGFR by Ͼ20% was associated with worse cardiovascular outcomes independently of baseline eGFR and of the use of eplerenone, which retained its prognostic benefits even under these circumstances. Conclusions-In patients with heart failure after acute myocardial infarction and receiving standard medical care, an early decline in eGFR is not uncommon and is associated with poor long-term outcome. Eplerenone induced a moderately more frequent early decline in eGFR, which did not affect its clinical benefit on cardiovascular outcomes. (Circulation. 2012;125:271-279.)Key Words: cardiorenal syndrome Ⅲ eplerenone Ⅲ kidney Ⅲ heart failure I mpaired renal function is a major adverse prognostic factor in acute and chronic heart failure (HF), 1-5 although most pharmacological treatments that improve the prognosis of patients with HF cause a decline in renal function. Clinical Perspective on p 279Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have prevented the progression of albuminuria and/or kidney dysfunction in various patient populations but may induce an acute deterioration in estimated glomerular filtration rate (eGFR) in HF patients. 6 -9 Mineralocorticoid receptor antagonists have also been shown to reduce proteinuria in patients with chronic kidney disease 10 -12 ; however, their long-term effect on renal function remains uncertain 10,11 and has not been reported in HF. The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) demonstrated that the addition of the low-dose mineralocorticoid receptor antagonist eplerenone to standard medical therapy in patients with acute myocardial infarction and HF with left Continuing medical education (CME) credit is available for this article. Go to ...

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In EMPHASIS-HF, eplerenone improved outcomes in HFrEF patients with and without abdominal obesity, although the benefit appeared to be more pronounced among those with abdominal obesity. The findings are potentially hypothesis generating and need to be replicated in other HFrEF populations.