Michael Walsh1, Braden Manns2, Amit X Garg3, Joe Bueti4, Christian Rabbat5, Andrew Smyth6, Jessica Tyrwhitt6, Jackie Bosch6, Peggy Gao6, P J Devereaux7, Ron Wald8. 1. 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. 2. Department of Medicine, Department of Community Health Sciences, Libin Cardiovascular Institute, and Institute of Public Health, University of Calgary, Calgary, Alberta, Canada; 3. Department of Medicine and Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada; 4. Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; 5. Department of Medicine and. 6. Population Health Research Institute, Hamilton Health Sciences/McMaster University, Hamilton, Ontario, Canada; 7. 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; 8. 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.
Abstract
BACKGROUND AND OBJECTIVES: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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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. CONCLUSION: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.
RCT Entities:
BACKGROUND AND OBJECTIVES: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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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. CONCLUSION: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.
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