The Safety and Efficacy of Mineralocorticoid Receptor Antagonists in Patients Who Require Dialysis: A Systematic Review and Meta-analysis.
BACKGROUND
Patients who require dialysis are at high risk for cardiovascular mortality, which may be improved by mineralocorticoid receptor antagonists (MRAs).


METHODS
Systematic review and meta-analysis of randomized controlled trials.


METHODS
Adults undergoing long-term hemodialysis or peritoneal dialysis with or without heart failure.


METHODS
Randomized controlled trials evaluating an MRA in dialysis and reported at least one outcome of interest.


METHODS
Spironolactone (8 trials) or eplerenone (1 trial) compared to placebo (7 trials) or standard of care (2 trials).


RESULTS
Cardiovascular and all-cause mortality, hyperkalemia, serum potassium level, hypotension, change in blood pressure, and gynecomastia.


RESULTS
We identified 9 trials including 829 patients. The overall quality of evidence was low due to methodologic limitations in most of the included trials. The relative risk (RR) for cardiovascular mortality was 0.34 (95% CI, 0.15-0.75) for MRA-treated compared with control patients. The RR for all-cause mortality was 0.40 (95% CI, 0.23-0.69). The RR for hyperkalemia for MRA treatment was 3.05 (95% CI, 1.21-7.70). Sensitivity analyses demonstrated wide variability in RRs for cardiovascular mortality, all-cause mortality, and hyperkalemia, suggesting further uncertainty in the confidence of the primary results.


CONCLUSIONS
Trial quality and size insufficient to robustly and precisely identify a treatment effect.


CONCLUSIONS
Given the uncertainty of both the benefits and harms of MRAs in dialysis, large high-quality trials are required.
Department of Clinical Epidemiology and Biostatistics, McMaster University, Ontario, Canada.
Kevin
K
Quach
Department of Clinical Epidemiology and Biostatistics, McMaster University, Ontario, Canada.
Lyubov
L
Lvtvyn
Clinical Trials Services Unit, Oxford University, Oxford, United Kingdom.
Colin
C
Baigent
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Joe
J
Bueti
Department of Medicine, Western University, London, Canada; Department of Epidemiology and Biostatistics, Western University, London, Canada.
Amit X
AX
Garg
Princess Alexandra Hospital, Woolloongabba, Queensland, Australia; University of Queensland, Brisbane, Queensland, Australia.
Carmel
C
Hawley
Clinical Trials Services Unit, Oxford University, Oxford, United Kingdom.
Richard
R
Haynes
Department of Medicine, University of Calgary, Calgary, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Canada.
Braden
B
Manns
George Institute for Global Health, Sydney, Australia.
Vlado
V
Perkovic
Department of Medicine, McMaster University, Ontario, Canada.
Christian G
CG
Rabbat
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Ron
R
Wald
Department of Clinical Epidemiology and Biostatistics, McMaster University, Ontario, Canada; Department of Medicine, McMaster University, Ontario, Canada; Population Health Research Institute, Hamilton Health Sciences/McMaster University, Ontario, Canada. Electronic address: lastwalsh1975@gmail.com.
Michael
M
Walsh
D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D002423:Cause of Death; D000077545:Eplerenone; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis; D013148:Spironolactone / Q000031:analogs & derivatives / Q000627:therapeutic use
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000077545:Eplerenone
Mineralocorticoid receptor antagonist (MRA); adverse events; aldosterone; all-cause mortality; blood pressure; cardiovascular death; end-stage renal disease (ESRD); eplerenone; hemodialysis; hyperkalemia; meta-analysis; peritoneal dialysis; randomized controlled trials; spironolactone; systematic review