title: The Safety of Eplerenone in Hemodialysis Patients: A Noninferiority Randomized Controlled Trial.
abstract: OBJECTIVE
  Mineralocorticoid receptor antagonism reduces morbidity and mortality in patients with heart failure, but the safety of these drugs in patients receiving dialysis is unclear. This study evaluated whether hyperkalemia and/or hypotension limited the use of eplerenone, a selective mineralocorticoid receptor antagonist, in hemodialysis patients.
  
  
  METHODS
  This was a randomized controlled trial of prevalent patients receiving hemodialysis at five Canadian centers. Participants were randomly allocated to 13 weeks of eplerenone titrated to 50 mg daily (n=77) or a matching placebo (n=77). The primary outcome was permanent discontinuation of the drug because of hyperkalemia or hypotension. Secondary outcomes included hyperkalemia, hypotension, and cardiovascular events.
  
  
  RESULTS
  Seventy-five eplerenone-treated patients and 71 placebo-treated patients were included in the per protocol population. The primary outcome occurred in three patients (4.0%) in the eplerenone group and two (2.8%) in the placebo group, for an absolute risk difference of 1.2 percentage points (95% confidence interval, -4.7 to 7.1 percentage points). Eplerenone was interpreted as noninferior to placebo with respect to the primary outcome (i.e., a discontinuation rate for these reasons >10% was excluded). In the eplerenone group, nine patients (11.7%) developed hyperkalemia (potassium level >6.5 mEq/L), compared with two patients (2.6%) in the placebo group (relative risk, 4.5; 95% confidence interval, 1.0 to 20.2). There was no significant effect on predialysis or postdialysis BP.
  
  
  CONCLUSIONS
  Eplerenone increased the risk of hyperkalemia but did not result in an excess need to permanently discontinue the drug. Further trials are required to determine whether mineralocorticoid receptor antagonism improves cardiovascular outcomes in patients receiving long-term dialysis.
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences/McMaster University, Hamilton, Ontario, Canada; Department of Medicine and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; lastwalsh1975@gmail.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Walsh
authors.affiliation: Department of Medicine, Department of Community Health Sciences, Libin Cardiovascular Institute, and Institute of Public Health, University of Calgary, Calgary, Alberta, Canada;
authors.forename: Braden
authors.initials: B
authors.lastname: Manns
authors.affiliation: Department of Medicine and Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada;
authors.forename: Amit X
authors.initials: AX
authors.lastname: Garg
authors.affiliation: Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada;
authors.forename: Joe
authors.initials: J
authors.lastname: Bueti
authors.affiliation: Department of Medicine and.
authors.forename: Christian
authors.initials: C
authors.lastname: Rabbat
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences/McMaster University, Hamilton, Ontario, Canada;
authors.forename: Andrew
authors.initials: A
authors.lastname: Smyth
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences/McMaster University, Hamilton, Ontario, Canada;
authors.forename: Jessica
authors.initials: J
authors.lastname: Tyrwhitt
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences/McMaster University, Hamilton, Ontario, Canada;
authors.forename: Jackie
authors.initials: J
authors.lastname: Bosch
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences/McMaster University, Hamilton, Ontario, Canada;
authors.forename: Peggy
authors.initials: P
authors.lastname: Gao
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences/McMaster University, Hamilton, Ontario, Canada; Department of Medicine and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada;
authors.forename: P J
authors.initials: PJ
authors.lastname: Devereaux
authors.affiliation: Department of Medicine, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada; and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Ron
authors.initials: R
authors.lastname: Wald
mesh_terms: D000368:Aged; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000077545:Eplerenone; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000097:blood / Q000139:chemically induced*; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D010865:Pilot Projects; D011188:Potassium / Q000097:blood; D006435:Renal Dialysis; D013148:Spironolactone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D028761:Withholding Treatment
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone; D011188:Potassium