title: The Effects of Cinacalcet in Older and Younger Patients on Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial.
abstract: OBJECTIVE
  The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older (≥65 years, n=1005) and younger (<65 years, n=2878) patients.
  
  
  METHODS
  Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.
  
  
  RESULTS
  Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were >3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups.
  
  
  CONCLUSIONS
  In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.
authors.affiliation: Department of Medicine, Health Sciences Center, St. John's, Newfoundland, Canada; pparfrey@mun.ca.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Parfrey
authors.affiliation: French Institute of Health and Medical Research Unit 1088, Faculty of Medicine and Pharmacy, University of Picardie, Amiens, France;
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drüeke
authors.affiliation: Denver Nephrology, Denver, Colorado;
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Block
authors.affiliation: Department of Nephrology and Mineral Metabolism, Salvador Zubirán National Institute of Health Sciences and Nutrition, Mexico City, Mexico;
authors.forename: Ricardo
authors.initials: R
authors.lastname: Correa-Rotter
authors.affiliation: Department of Nephrology, RWTH Aachen University Hospital, Aachen, Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: Department of Internal Medicine, University of Minnesota, Minneapolis, Minnesota;
authors.forename: Charles A
authors.initials: CA
authors.lastname: Herzog
authors.affiliation: Service of Nephrology, Manhès Hospital, Paris, France;
authors.forename: Gerard M
authors.initials: GM
authors.lastname: London
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Palo Alto, California;
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Department of Medicine, Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis, Indiana;
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.affiliation: Centre for Nephrology, University College London, United Kingdom; and.
authors.forename: David C
authors.initials: DC
authors.lastname: Wheeler
authors.affiliation: Amgen Inc, Thousand Oaks, California.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kubo
authors.affiliation: Amgen Inc, Thousand Oaks, California.
authors.forename: Bastian
authors.initials: B
authors.lastname: Dehmel
authors.affiliation: Amgen Inc, Thousand Oaks, California.
authors.forename: William G
authors.initials: WG
authors.lastname: Goodman
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Palo Alto, California;
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D057966:Calcimimetic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D000069449:Cinacalcet / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000150:complications / Q000401:mortality* / Q000628:therapy; D016030:Kidney Transplantation / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D016105:Parathyroidectomy / Q000706:statistics & numerical data; D006435:Renal Dialysis; D012720:Severity of Illness Index
chemical_list: D057966:Calcimimetic Agents; D000069449:Cinacalcet
keywords: CKD; cardiovascular disease; hemodialysis; hyperparathyroidism; mineral metabolism