title: The Effect of Cinacalcet on Calcific Uremic Arteriolopathy Events in Patients Receiving Hemodialysis: The EVOLVE Trial.
abstract: OBJECTIVE
  Uncontrolled secondary hyperparathyroidism (sHPT) in patients with ESRD is a risk factor for calcific uremic arteriolopathy (CUA; calciphylaxis).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Cinacalcet appeared to reduce the incidence of CUA in hemodialysis recipients who have moderate to severe sHPT.
authors.affiliation: Division of Nephrology, RWTH University of Aachen, Aachen, Germany; Juergen.floege@rwth-aachen.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: Amgen Inc., Thousand Oaks, California;
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kubo
authors.affiliation: Division of Nephrology, RWTH University of Aachen, Aachen, Germany;
authors.forename: Anna
authors.initials: A
authors.lastname: Floege
authors.affiliation: Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Palo Alto, California; and.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
authors.affiliation: Department of Medicine, Memorial University, St. John's, Newfoundland, Canada.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Parfrey
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure; D015992:Body Mass Index; D057966:Calcimimetic Agents / Q000627:therapeutic use*; D002115:Calciphylaxis / Q000453:epidemiology* / Q000209:etiology; D000069449:Cinacalcet / Q000627:therapeutic use*; D050171:Dyslipidemias / Q000453:epidemiology; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D016105:Parathyroidectomy; D006435:Renal Dialysis; D012307:Risk Factors; D012737:Sex Factors; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D057966:Calcimimetic Agents; D010281:Parathyroid Hormone; D014812:Vitamin K; D000069449:Cinacalcet
keywords: calcium receptor; dialysis; hyperparathyroidism; hyperphosphatemia; mineral metabolism