Spironolactone Reduces Cardiovascular and Cerebrovascular Morbidity and Mortality in Hemodialysis Patients

OBJECTIVES: This study sought to assess whether spironolactone treatment reduces the high incidence of cardiovascular and cerebrovascular (CCV) morbidity and mortality in hemodialysis (HD) patients. BACKGROUND: Aldosterone receptor blockers reduce cardiac-related events, but the efficacy of the agents in HD patients is unclear. METHODS: A 3-year randomized trial involving 5 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. RESULTS: 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 the primary outcome for treatment were 0.404 (95% confidence interval CI: 0.202 to 0.809; p = 0.017) and 0.379 (95% CI: 0.173 to 0.832; p = 0.016) before and after adjustment, respectively. The secondary outcome was significantly reduced in the treatment group compared with the control group (6.4% vs. 19.7%; HRs: 0.355 95% CI: 0.191 to 0.662; p = 0.002 and 0.335 95% CI: 0.162 to 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 3 patients (1.9%). CONCLUSIONS: Aldosterone receptor blockade using spironolactone may substantially reduce the risk of both CCV morbidity and death among HD patients; however, larger-scale studies are recommended to further confirm its efficacy. (Effects of Spironolactone on Cardio- and Cerebrovascular Morbidity and Mortality in Hemodialysis Patients; NCT01687699).