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

Research output: Contribution to journalArticleAcademicpeer-review

139 Citations (Scopus)


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: Unique identifier: NCT00232180.

Original languageEnglish
Pages (from-to)51-58
Number of pages8
JournalCirculation-Heart failure
Issue number1
Publication statusPublished - Jan-2014


  • heart failure
  • kidney
  • potassium
  • prognosis

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