title: Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis: The EVOLVE Trial.
abstract: Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%-29%.
authors.affiliation: Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis, Indiana; smoe@iupui.edu.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.affiliation: Stanford University School of Medicine, Palo Alto, California;
authors.forename: Safa
authors.initials: S
authors.lastname: Abdalla
authors.affiliation: Stanford University School of Medicine, Palo Alto, California;
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
authors.affiliation: Health Sciences Center, St. John's, Newfoundland, Canada;
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Parfrey
authors.affiliation: Denver Nephrology, Denver, Colorado;
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Block
authors.affiliation: Salvador Zubirán National Institute of Medical Sciences and Nutrition, Mexico City, Mexico;
authors.forename: Ricardo
authors.initials: R
authors.lastname: Correa-Rotter
authors.affiliation: University Hospital RWTH Aachen, Aachen, Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: University of Minnesota, Minneapolis, Minnesota;
authors.forename: Charles A
authors.initials: CA
authors.lastname: Herzog
authors.affiliation: Manhès Hospital, Paris, France;
authors.forename: Gerard M
authors.initials: GM
authors.lastname: London
authors.affiliation: Stanford University School of Medicine, Palo Alto, California;
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: University College London, London, United Kingdom;
authors.forename: David C
authors.initials: DC
authors.lastname: Wheeler
authors.affiliation: Amgen Inc., Thousand Oaks, California; and.
authors.forename: Bastian
authors.initials: B
authors.lastname: Dehmel
authors.affiliation: Amgen Inc., Thousand Oaks, California; and.
authors.forename: William G
authors.initials: WG
authors.lastname: Goodman
authors.affiliation: French Institute of Health and Medical Research (INSERM) Unit 1088, Faculty of Medicine/Pharmacy, University of Picardie, Amiens, France.
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drüeke
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000069449:Cinacalcet; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012016:Reference Values; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods; D018570:Risk Assessment; D012737:Sex Factors; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D009281:Naphthalenes; D000069449:Cinacalcet
keywords: CKD; hemodialysis; hyperparathyroidism; osteodystrophy; renal