Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study

Patrick Rossignol; John G F Cleland; Sunil Bhandari; Stéphane Tala; Finn Gustafsson; Renaud Fay; Zohra Lamiral; Daniela Dobre; Bertram Pitt; Faiez Zannad

doi:10.1161/CIRCULATIONAHA.111.028282

Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study

Patrick Rossignol, John G F Cleland, Sunil Bhandari, Stéphane Tala, Finn Gustafsson, Renaud Fay, Zohra Lamiral, Daniela Dobre, Bertram Pitt, Faiez Zannad

95 Citations (Scopus)

Abstract

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 -1.4±0.3 mL · min ^-1 · 1.73 m ^-2 compared with placebo (P<0.0001), an effect that appeared within the first month (-1.3±0.4 mL · min ^-1 · 1.73 m ^-2) and persisted throughout the study. Overall, 914 patients experienced a decline in eGFR >20% 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; P=0.017). In multivariate analyses, determinants of this early decline in eGFR were female sex, age ≥65 years, smoking, left ventricular ejection fraction <35%, and use of eplerenone and loop diuretic. An early decline in eGFR by >20% 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.

Original language	English
Journal	Circulation
Volume	125
Issue number	2
Pages (from-to)	271-9
Number of pages	9
ISSN	0009-7322
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.111.028282
Publication status	Published - 17 Jan 2012

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Rossignol, P., Cleland, J. G. F., Bhandari, S., Tala, S., Gustafsson, F., Fay, R., Lamiral, Z., Dobre, D., Pitt, B., & Zannad, F. (2012). Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study. Circulation, 125(2), 271-9. https://doi.org/10.1161/CIRCULATIONAHA.111.028282

Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction : insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study. / Rossignol, Patrick; Cleland, John G F; Bhandari, Sunil et al.

In: Circulation, Vol. 125, No. 2, 17.01.2012, p. 271-9.

Research output: Contribution to journal › Journal article › Research › peer-review

Rossignol, P, Cleland, JGF, Bhandari, S, Tala, S, Gustafsson, F, Fay, R, Lamiral, Z, Dobre, D, Pitt, B & Zannad, F 2012, 'Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study', Circulation, vol. 125, no. 2, pp. 271-9. https://doi.org/10.1161/CIRCULATIONAHA.111.028282

Rossignol P, Cleland JGF, Bhandari S, Tala S, Gustafsson F, Fay R et al. Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study. Circulation. 2012 Jan 17;125(2):271-9. doi: 10.1161/CIRCULATIONAHA.111.028282

Rossignol, Patrick ; Cleland, John G F ; Bhandari, Sunil et al. / Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction : insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study. In: Circulation. 2012 ; Vol. 125, No. 2. pp. 271-9.

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title = "Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study",

abstract = "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 -1.4±0.3 mL · min -1 · 1.73 m -2 compared with placebo (P<0.0001), an effect that appeared within the first month (-1.3±0.4 mL · min -1 · 1.73 m -2) and persisted throughout the study. Overall, 914 patients experienced a decline in eGFR >20% 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; P=0.017). In multivariate analyses, determinants of this early decline in eGFR were female sex, age ≥65 years, smoking, left ventricular ejection fraction <35%, and use of eplerenone and loop diuretic. An early decline in eGFR by >20% 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.",

author = "Patrick Rossignol and Cleland, {John G F} and Sunil Bhandari and St{\'e}phane Tala and Finn Gustafsson and Renaud Fay and Zohra Lamiral and Daniela Dobre and Bertram Pitt and Faiez Zannad",

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T1 - Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction

T2 - insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study

AU - Rossignol, Patrick

AU - Cleland, John G F

AU - Bhandari, Sunil

AU - Tala, Stéphane

AU - Gustafsson, Finn

AU - Fay, Renaud

AU - Lamiral, Zohra

AU - Dobre, Daniela

AU - Pitt, Bertram

AU - Zannad, Faiez

PY - 2012/1/17

Y1 - 2012/1/17

N2 - 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 -1.4±0.3 mL · min -1 · 1.73 m -2 compared with placebo (P<0.0001), an effect that appeared within the first month (-1.3±0.4 mL · min -1 · 1.73 m -2) and persisted throughout the study. Overall, 914 patients experienced a decline in eGFR >20% 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; P=0.017). In multivariate analyses, determinants of this early decline in eGFR were female sex, age ≥65 years, smoking, left ventricular ejection fraction <35%, and use of eplerenone and loop diuretic. An early decline in eGFR by >20% 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.

AB - 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 -1.4±0.3 mL · min -1 · 1.73 m -2 compared with placebo (P<0.0001), an effect that appeared within the first month (-1.3±0.4 mL · min -1 · 1.73 m -2) and persisted throughout the study. Overall, 914 patients experienced a decline in eGFR >20% 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; P=0.017). In multivariate analyses, determinants of this early decline in eGFR were female sex, age ≥65 years, smoking, left ventricular ejection fraction <35%, and use of eplerenone and loop diuretic. An early decline in eGFR by >20% 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.

U2 - 10.1161/CIRCULATIONAHA.111.028282

DO - 10.1161/CIRCULATIONAHA.111.028282

M3 - Journal article

C2 - 22128223

SN - 0009-7322

VL - 125

SP - 271

EP - 279

JO - Circulation

JF - Circulation

IS - 2

ER -