Incidence, Determinants, and Prognostic Significance of Hyperkalemia and Worsening Renal Function in Patients With Heart Failure Receiving the Mineralocorticoid Receptor Antagonist Eplerenone or Placebo in Addition to Optimal Medical Therapy Results From the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF)

Patrick Rossignol; Daniela Dobre; John J. V. McMurray; Karl Swedberg; Henry Krum; Dirk J. van Veldhuisen; Harry Shi; Michael Messig; John Vincent; Nicolas Girerd; George Bakris; Bertram Pitt; Faiez Zannad

doi:10.1161/CIRCHEARTFAILURE.113.000792

Incidence, Determinants, and Prognostic Significance of Hyperkalemia and Worsening Renal Function in Patients With Heart Failure Receiving the Mineralocorticoid Receptor Antagonist Eplerenone or Placebo in Addition to Optimal Medical Therapy Results From the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF)

Patrick Rossignol
, Daniela Dobre
, John J. V. McMurray
, Karl Swedberg
, Henry Krum
, Dirk J. van Veldhuisen
, Harry Shi
, Michael Messig
, John Vincent
, Nicolas Girerd
, George Bakris
, Bertram Pitt
, Faiez Zannad^*

^*Corresponding author for this work

Cardiovascular Centre (CVC)

Research output: Contribution to journal › Article › Academic › peer-review

231 Citations (Scopus)

Abstract

Background Mineralocorticoid receptor antagonists improve outcomes in patients with systolic heart failure but may induce worsening of renal function (WRF) and hyperkalemia (HK). We assessed the risk factors for mineralocorticoid receptor antagonist-related WRF and for HK, as well as the association between HK and WRF with clinical outcomes in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF).

Methods and Results Serial changes in estimated glomerular filtration rate and in serum potassium were available in 2737 patients during a median 21-month follow-up. HK variably defined as serum K >4.5, 5, or 5.5 mmol/L occurred in 74.7%, 32.5%, and 8.9% patients enrolled in EMPHASIS-HF, respectively. WRF defined as a decrease in estimated glomerular filtration rate >20% or >30% from baseline occurred in 27% and 14% of patients, respectively. Patients assigned eplerenone displayed modest and early but significant and persistent (1) rise in serum potassium and (2) reduction in estimated glomerular filtration rate when compared with those assigned placebo. In multivariate analyses, eplerenone was associated with a higher incidence of WRF and HK, which were interrelated and also associated with baseline patient characteristics (eg, age 75 years, hypertension, diabetes mellitus, nonwhite race, ejection fraction 5.5 mmol/L only and WRF and worse outcomes.

Conclusions In patients with heart failure receiving optimal therapy, WRF and HK were more frequent when eplerenone was added, but their occurrence did not eliminate the survival benefit of eplerenone.

Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.

Original language	English
Pages (from-to)	51-58
Number of pages	8
Journal	Circulation-Heart failure
Volume	7
Issue number	1
DOIs	https://doi.org/10.1161/CIRCHEARTFAILURE.113.000792
Publication status	Published - Jan-2014

Keywords

heart failure
kidney
potassium
prognosis
ASSOCIATION TASK-FORCE
MYOCARDIAL-INFARCTION
PRACTICE GUIDELINES
SYSTOLIC DYSFUNCTION
EFFICACY
OUTCOMES
COLLABORATION
METAANALYSIS
MANAGEMENT
DIAGNOSIS

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Rossignol, P., Dobre, D., McMurray, J. J. V., Swedberg, K., Krum, H., van Veldhuisen, D. J., Shi, H., Messig, M., Vincent, J., Girerd, N., Bakris, G., Pitt, B., & Zannad, F. (2014). Incidence, Determinants, and Prognostic Significance of Hyperkalemia and Worsening Renal Function in Patients With Heart Failure Receiving the Mineralocorticoid Receptor Antagonist Eplerenone or Placebo in Addition to Optimal Medical Therapy Results From the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). Circulation-Heart failure, 7(1), 51-58. https://doi.org/10.1161/CIRCHEARTFAILURE.113.000792

Rossignol, Patrick ; Dobre, Daniela ; McMurray, John J. V. et al. / Incidence, Determinants, and Prognostic Significance of Hyperkalemia and Worsening Renal Function in Patients With Heart Failure Receiving the Mineralocorticoid Receptor Antagonist Eplerenone or Placebo in Addition to Optimal Medical Therapy Results From the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). In: Circulation-Heart failure. 2014 ; Vol. 7, No. 1. pp. 51-58.

@article{d75c031b91d54050b415d39e81d13d64,

title = "Incidence, Determinants, and Prognostic Significance of Hyperkalemia and Worsening Renal Function in Patients With Heart Failure Receiving the Mineralocorticoid Receptor Antagonist Eplerenone or Placebo in Addition to Optimal Medical Therapy Results From the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF)",

abstract = "Background Mineralocorticoid receptor antagonists improve outcomes in patients with systolic heart failure but may induce worsening of renal function (WRF) and hyperkalemia (HK). We assessed the risk factors for mineralocorticoid receptor antagonist-related WRF and for HK, as well as the association between HK and WRF with clinical outcomes in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF).Methods and Results Serial changes in estimated glomerular filtration rate and in serum potassium were available in 2737 patients during a median 21-month follow-up. HK variably defined as serum K >4.5, 5, or 5.5 mmol/L occurred in 74.7\%, 32.5\%, and 8.9\% patients enrolled in EMPHASIS-HF, respectively. WRF defined as a decrease in estimated glomerular filtration rate >20\% or >30\% from baseline occurred in 27\% and 14\% of patients, respectively. Patients assigned eplerenone displayed modest and early but significant and persistent (1) rise in serum potassium and (2) reduction in estimated glomerular filtration rate when compared with those assigned placebo. In multivariate analyses, eplerenone was associated with a higher incidence of WRF and HK, which were interrelated and also associated with baseline patient characteristics (eg, age 75 years, hypertension, diabetes mellitus, nonwhite race, ejection fraction 5.5 mmol/L only and WRF and worse outcomes.Conclusions In patients with heart failure receiving optimal therapy, WRF and HK were more frequent when eplerenone was added, but their occurrence did not eliminate the survival benefit of eplerenone.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.",

keywords = "heart failure, kidney, potassium, prognosis, ASSOCIATION TASK-FORCE, MYOCARDIAL-INFARCTION, PRACTICE GUIDELINES, SYSTOLIC DYSFUNCTION, EFFICACY, OUTCOMES, COLLABORATION, METAANALYSIS, MANAGEMENT, DIAGNOSIS",

author = "Patrick Rossignol and Daniela Dobre and McMurray, \{John J. V.\} and Karl Swedberg and Henry Krum and \{van Veldhuisen\}, \{Dirk J.\} and Harry Shi and Michael Messig and John Vincent and Nicolas Girerd and George Bakris and Bertram Pitt and Faiez Zannad",

year = "2014",

month = jan,

doi = "10.1161/CIRCHEARTFAILURE.113.000792",

language = "English",

volume = "7",

pages = "51--58",

journal = "Circulation-Heart failure",

issn = "1941-3289",

publisher = "Lippincott Williams and Wilkins",

number = "1",

}

Rossignol, P, Dobre, D, McMurray, JJV, Swedberg, K, Krum, H, van Veldhuisen, DJ, Shi, H, Messig, M, Vincent, J, Girerd, N, Bakris, G, Pitt, B & Zannad, F 2014, 'Incidence, Determinants, and Prognostic Significance of Hyperkalemia and Worsening Renal Function in Patients With Heart Failure Receiving the Mineralocorticoid Receptor Antagonist Eplerenone or Placebo in Addition to Optimal Medical Therapy Results From the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF)', Circulation-Heart failure, vol. 7, no. 1, pp. 51-58. https://doi.org/10.1161/CIRCHEARTFAILURE.113.000792

Incidence, Determinants, and Prognostic Significance of Hyperkalemia and Worsening Renal Function in Patients With Heart Failure Receiving the Mineralocorticoid Receptor Antagonist Eplerenone or Placebo in Addition to Optimal Medical Therapy Results From the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). / Rossignol, Patrick; Dobre, Daniela; McMurray, John J. V. et al.
In: Circulation-Heart failure, Vol. 7, No. 1, 01.2014, p. 51-58.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Incidence, Determinants, and Prognostic Significance of Hyperkalemia and Worsening Renal Function in Patients With Heart Failure Receiving the Mineralocorticoid Receptor Antagonist Eplerenone or Placebo in Addition to Optimal Medical Therapy Results From the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF)

AU - Rossignol, Patrick

AU - Dobre, Daniela

AU - McMurray, John J. V.

AU - Swedberg, Karl

AU - Krum, Henry

AU - van Veldhuisen, Dirk J.

AU - Shi, Harry

AU - Messig, Michael

AU - Vincent, John

AU - Girerd, Nicolas

AU - Bakris, George

AU - Pitt, Bertram

AU - Zannad, Faiez

PY - 2014/1

Y1 - 2014/1

N2 - Background Mineralocorticoid receptor antagonists improve outcomes in patients with systolic heart failure but may induce worsening of renal function (WRF) and hyperkalemia (HK). We assessed the risk factors for mineralocorticoid receptor antagonist-related WRF and for HK, as well as the association between HK and WRF with clinical outcomes in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF).Methods and Results Serial changes in estimated glomerular filtration rate and in serum potassium were available in 2737 patients during a median 21-month follow-up. HK variably defined as serum K >4.5, 5, or 5.5 mmol/L occurred in 74.7%, 32.5%, and 8.9% patients enrolled in EMPHASIS-HF, respectively. WRF defined as a decrease in estimated glomerular filtration rate >20% or >30% from baseline occurred in 27% and 14% of patients, respectively. Patients assigned eplerenone displayed modest and early but significant and persistent (1) rise in serum potassium and (2) reduction in estimated glomerular filtration rate when compared with those assigned placebo. In multivariate analyses, eplerenone was associated with a higher incidence of WRF and HK, which were interrelated and also associated with baseline patient characteristics (eg, age 75 years, hypertension, diabetes mellitus, nonwhite race, ejection fraction 5.5 mmol/L only and WRF and worse outcomes.Conclusions In patients with heart failure receiving optimal therapy, WRF and HK were more frequent when eplerenone was added, but their occurrence did not eliminate the survival benefit of eplerenone.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.

AB - Background Mineralocorticoid receptor antagonists improve outcomes in patients with systolic heart failure but may induce worsening of renal function (WRF) and hyperkalemia (HK). We assessed the risk factors for mineralocorticoid receptor antagonist-related WRF and for HK, as well as the association between HK and WRF with clinical outcomes in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF).Methods and Results Serial changes in estimated glomerular filtration rate and in serum potassium were available in 2737 patients during a median 21-month follow-up. HK variably defined as serum K >4.5, 5, or 5.5 mmol/L occurred in 74.7%, 32.5%, and 8.9% patients enrolled in EMPHASIS-HF, respectively. WRF defined as a decrease in estimated glomerular filtration rate >20% or >30% from baseline occurred in 27% and 14% of patients, respectively. Patients assigned eplerenone displayed modest and early but significant and persistent (1) rise in serum potassium and (2) reduction in estimated glomerular filtration rate when compared with those assigned placebo. In multivariate analyses, eplerenone was associated with a higher incidence of WRF and HK, which were interrelated and also associated with baseline patient characteristics (eg, age 75 years, hypertension, diabetes mellitus, nonwhite race, ejection fraction 5.5 mmol/L only and WRF and worse outcomes.Conclusions In patients with heart failure receiving optimal therapy, WRF and HK were more frequent when eplerenone was added, but their occurrence did not eliminate the survival benefit of eplerenone.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.

KW - heart failure

KW - kidney

KW - potassium

KW - prognosis

KW - ASSOCIATION TASK-FORCE

KW - MYOCARDIAL-INFARCTION

KW - PRACTICE GUIDELINES

KW - SYSTOLIC DYSFUNCTION

KW - EFFICACY

KW - OUTCOMES

KW - COLLABORATION

KW - METAANALYSIS

KW - MANAGEMENT

KW - DIAGNOSIS

U2 - 10.1161/CIRCHEARTFAILURE.113.000792

DO - 10.1161/CIRCHEARTFAILURE.113.000792

M3 - Article

SN - 1941-3289

VL - 7

SP - 51

EP - 58

JO - Circulation-Heart failure

JF - Circulation-Heart failure

IS - 1

ER -

Rossignol P, Dobre D, McMurray JJV, Swedberg K, Krum H, van Veldhuisen DJ et al. Incidence, Determinants, and Prognostic Significance of Hyperkalemia and Worsening Renal Function in Patients With Heart Failure Receiving the Mineralocorticoid Receptor Antagonist Eplerenone or Placebo in Addition to Optimal Medical Therapy Results From the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). Circulation-Heart failure. 2014 Jan;7(1):51-58. doi: 10.1161/CIRCHEARTFAILURE.113.000792