A Randomized, Double-Blind, Placebo-Controlled Trial of Spironolactone on Carotid Intima-Media Thickness in Nondiabetic Hemodialysis Patients

Abstract

Background and objectives: Hemodialysis patients (HD) display high rates of cardiac diseases and mortality. In chronic kidney disease, vascular injury leads to coronary artery disease, heart failure, and stroke. Carotid intima-media thickness (CIMT) measurements are currently widely used in randomized controlled trials (RCTs) to study the efficacy of interventions. An RCT was designed for the assessment of the safety and effectiveness of spironolactone to inhibit the progression of CIMT in HD patients as a primary outcome. Secondary outcomes included measurements of plasma potassium.Design, setting, participants, & measurements: HD patients were randomly assigned to receive 50 mg spironolactone or placebo thrice weekly after dialysis. In between dialysis sessions, plasma potassium concentrations were measured every month. Ultrasonographic measurements of CIMT were done at the beginning of the study and after 2 years.Results: Fifty-three age-and sex-adjusted patients (30 with drug and 23 with placebo) successfully completed the trial. There were no significant differences between the two groups in all profiles studied at baseline. Measurements of CIMT after 2 years showed a progression in the placebo group, whereas in the spironolactone group a significant decrease or even reversed CIMT was observed. Progression rates (mm/yr) were: common carotid, placebo: 0.06 ؎ 0.07, spironolactone: 0.01 ؎ 0.04; carotid bifurcation, placebo: 0.15 ؎ 0.27, spironolactone: 0.0001 ؎ 0.01; internal carotid, placebo: 0.10 ؎ 0.12, spironolactone: ؊0.10 ؎ 0.15. No episodes of hyperkalemia were observed, but a slight increase in plasma potassium was found in the spironolactone group.Conclusions: Fifty milligrams of spironolactone thrice weekly significantly reduced the progression of CIMT in HD patients.

Safety and cardiovascular effects of mineralocorticoid receptor antagonists for patients receiving hemodialysis: a systematic review and meta-analysis

“…After full-text screening, one article was excluded as no data of serum potassium for the control group was provided. 21 Eleven studies were reported in this systematic review, among which five studies were RCTs [22][23][24][25][26] and six were non-randomized studies [27][28][29][30][31][32] ( Figure 1). …”

Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology

“…In human hypertensive patients, MRA improved flow-mediated dilation, a mechanism contributing to vascular tone in hypertension (Fujimura et al, 2012). In patients with end-stage renal disease (ESRD), MRA also had favorable effects on intima-media remodeling (Vukusich et al, 2010). Of note, two studies reported a nondiuretic effect on blood pressure in patients with ESRD treated with spironolactone or eplerenone (Gross et al, 2005;Shavit et al, 2012).…”

Cardiovascular actions of mineralocorticoid receptor antagonists in patients with chronic kidney disease: A systematic review and meta-analysis of randomized trials

“…Spironolactone thrice weekly post-dialysis was shown to significantly reduce the progression of CIMT after two years as compared with placebo. 42 …”