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).
  
  
  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<30%, and treatment with an antiarrythmics drug or loop diuretic). Eplerenone retained its survival benefits without any significant interaction with the association between HK>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.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.
authors.affiliation: Inserm, Centre d'Investigations Cliniques- 9501, and Inserm U1116, Nancy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.forename: Daniela
authors.initials: D
authors.lastname: Dobre
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Karl
authors.initials: K
authors.lastname: Swedberg
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: Harry
authors.initials: H
authors.lastname: Shi
authors.forename: Michael
authors.initials: M
authors.lastname: Messig
authors.forename: John
authors.initials: J
authors.lastname: Vincent
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girerd
authors.forename: George
authors.initials: G
authors.lastname: Bakris
authors.forename: Bertram
authors.initials: B
authors.lastname: Pitt
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
mesh_terms: D058186:Acute Kidney Injury / Q000453:epidemiology* / Q000503:physiopathology; D000368:Aged; D000369:Aged, 80 and over; D000077545:Eplerenone; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D006947:Hyperkalemia / Q000097:blood / Q000453:epidemiology*; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D015999:Multivariate Analysis; D011188:Potassium / Q000097:blood; D011379:Prognosis; D012307:Risk Factors; D013148:Spironolactone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015996:Survival Rate
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D011188:Potassium
keywords: heart failure; kidney; potassium; prognosis