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.

Figure 1.

Trial profile. The reason for patients withdrew is given in the frame boxes.

Figure 2.

Progression rate in CIMT (mm) after 2 years of follow-up in HD patients. Analysis with t test for Δ by treatment group: (a) placebo, (b) spironolactone. A, right CCA (P < 0.03, power 0.56); B, right ICA (P < 0.0001, power 0.99); C, right BIF (P < 0.0001, power 0.92); D, left CCA (P < 0.0001, power 0.99); E, left ICA (P < 0.04, power 0.45); F, left BIF (P < 0.0001, power 0.98). The graph box plot represents median, interquartile range, and outer layer thickness.

Figure 3.

Plasma potassium values in each month during 24 months for patients with spironolactone (closed circles) or placebo (open circles). Values expressed as mean ± SD. *P < 0.05. Insert: GEE population-averaged model predicts a monthly increase in plasma potassium concentration of 0.018 mEq/L with spironolactone treatment.