TY - JOUR
T1 - The Safety and Efficacy of Mineralocorticoid Receptor Antagonists in Patients Who Require Dialysis
T2 - A Systematic Review and Meta-analysis
AU - Quach, Kevin
AU - Lvtvyn, Lyubov
AU - Baigent, Colin
AU - Bueti, Joe
AU - Garg, Amit X.
AU - Hawley, Carmel
AU - Haynes, Richard
AU - Manns, Braden
AU - Perkovic, Vlado
AU - Rabbat, Christian G.
AU - Wald, Ron
AU - Walsh, Michael
N1 - Funding Information:
Support: No sponsor was involved in this study. Dr Walsh is supported by a Canadian Institutes of Health Research New Investigator Award. Dr Garg received salary support from the Academic Medical Organization of Southwestern Ontario .
Publisher Copyright:
© 2016 The Authors
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Background Patients who require dialysis are at high risk for cardiovascular mortality, which may be improved by mineralocorticoid receptor antagonists (MRAs). Study Design Systematic review and meta-analysis of randomized controlled trials. Setting & Population Adults undergoing long-term hemodialysis or peritoneal dialysis with or without heart failure. Selection Criteria for Studies Randomized controlled trials evaluating an MRA in dialysis and reported at least one outcome of interest. Intervention Spironolactone (8 trials) or eplerenone (1 trial) compared to placebo (7 trials) or standard of care (2 trials). Outcomes 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. Limitations 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.
AB - Background Patients who require dialysis are at high risk for cardiovascular mortality, which may be improved by mineralocorticoid receptor antagonists (MRAs). Study Design Systematic review and meta-analysis of randomized controlled trials. Setting & Population Adults undergoing long-term hemodialysis or peritoneal dialysis with or without heart failure. Selection Criteria for Studies Randomized controlled trials evaluating an MRA in dialysis and reported at least one outcome of interest. Intervention Spironolactone (8 trials) or eplerenone (1 trial) compared to placebo (7 trials) or standard of care (2 trials). Outcomes 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. Limitations 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.
KW - Mineralocorticoid receptor antagonist (MRA)
KW - adverse events
KW - aldosterone
KW - all-cause mortality
KW - blood pressure
KW - cardiovascular death
KW - end-stage renal disease (ESRD)
KW - eplerenone
KW - hemodialysis
KW - hyperkalemia
KW - meta-analysis
KW - peritoneal dialysis
KW - randomized controlled trials
KW - spironolactone
KW - systematic review
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U2 - 10.1053/j.ajkd.2016.04.011
DO - 10.1053/j.ajkd.2016.04.011
M3 - Article
C2 - 27265777
AN - SCOPUS:84975704707
SN - 0272-6386
VL - 68
SP - 591
EP - 598
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 4
ER -