The Effect of Cinacalcet on Calcific Uremic Arteriolopathy Events in Patients Receiving Hemodialysis: The EVOLVE Trial

Abstract

Background and objectives: Uncontrolled secondary hyperparathyroidism (sHPT) in patients with ESRD is a risk factor for calcific uremic arteriolopathy (CUA; calciphylaxis).

Design, setting, participants, & measurements: Adverse event reports collected during the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial were used to determine the frequency of CUA in patients receiving hemodialysis who had moderate to severe sHPT, as well as the effects of cinacalcet versus placebo. CUA events were collected while patients were receiving the study drug.

Results: Among the 3861 trial patients who received at least one dose of the study drug, 18 patients randomly assigned to placebo and six assigned to cinacalcet developed CUA (unadjusted relative hazard, 0.31; 95% confidence interval [95% CI], 0.13 to 0.79; P=0.014). Corresponding cumulative event rates (95% CI) at year 4 were 0.011% (0.006% to 0.018%) and 0.005% (0.002% to 0.010%). By multivariable analysis, other factors associated with CUA included female sex, higher body mass index, higher diastolic BP, and history of dyslipidemia or parathyroidectomy. Median (10%, 90% percentile) plasma parathyroid hormone concentrations proximal to the report of CUA were 796 (225, 2093) pg/ml and 410 (71, 4957) pg/ml in patients randomly assigned to placebo and cinacalcet, respectively. Active use of vitamin K antagonists was recorded in 11 of 24 patients with CUA, nine randomly assigned to placebo, and two to cinacalcet, in contrast to 5%-7% at any one time point in patients in whom CUA was not reported.

Conclusion: Cinacalcet appeared to reduce the incidence of CUA in hemodialysis recipients who have moderate to severe sHPT.

Trial registration: ClinicalTrials.gov NCT00345839.

Keywords: calcium receptor; dialysis; hyperparathyroidism; hyperphosphatemia; mineral metabolism.

Copyright © 2015 by the American Society of Nephrology.

Figures

Figure 1.

Cumulative incidence plot of time to calcific uremic arteriolopathyadverse event (safety analysis set).