Spironolactone Reduces Cardio- and Cerebrovascular Morbidity and Mortality in Hemodialysis Patients

Study Questions:

What is the effect of spironolactone treatment on the incidence of cardiovascular and cerebrovascular (CCV) morbidity and mortality in hemodialysis (HD) patients?


A 3-year randomized trial involving five clinics was performed. Of the 309 oligoanuric HD patients enrolled in the study, 157 patients were randomly assigned to receive 25 mg/day of spironolactone without any restriction on dietary potassium intake (treatment group), and 152 patients were assigned to a control group. The primary outcome was a composite of death from CCV events or hospitalization for CCV events, and the secondary outcome was death from all causes.


During the 3-year follow-up, the primary outcome occurred in 5.7% of patients in the treatment group and in 12.5% of patients in the control group. Hazard ratios (HRs) for treatment were 0.404 (95% confidence interval [CI], 0.202-0.809; p = 0.017) and 0.379 (95% CI, 0.173-0.832; p = 0.016) before and after adjustment, respectively. The secondary outcome was also significantly reduced in the treatment group compared with the control group (6.4% vs. 19.7%; HRs, 0.355 [95% CI, 0.191-0.662; p = 0.002] and 0.335 [95% CI, 0.162-0.693; p = 0.003] before and after adjustment, respectively). Gynecomastia or breast pain was reported in 16 patients (10.2%) in the treatment group. Serious hyperkalemia led to treatment discontinuation in three patients (1.9%).


The authors concluded that aldosterone receptor blockade using spironolactone may substantially reduce the risk of both CCV morbidity and death among HD patients.


This study reported that low-dose spironolactone can be safely administered for a long duration to HD patients, and it may potentially reduce CCV events and all-cause mortality. While spironolactone may be a useful therapy for improving the currently poor prognosis for HD patients, larger-scale studies are necessary to confirm these findings given the small sample size and differences between the groups including duration of dialysis in the current study. The ongoing ALCHEMIST (ALdosterone antagonist Chronic HEModialysis Interventional STudy) trial will provide additional insight regarding cardiovascular benefits with aldosterone antagonists in high-risk patients with end-stage renal disease on HD.

Keywords: Follow-Up Studies, Morbidity, Kidney Failure, Chronic, Mineralocorticoid Receptor Antagonists, Diuretics, Hyperkalemia, Spironolactone, Signal Transduction, Gynecomastia, Prognosis, Renal Dialysis, Receptors, Mineralocorticoid, Mastodynia, Cardiovascular Diseases, Potassium, Dietary, Confidence Intervals, Renal Insufficiency, Chronic

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