title: Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial.
abstract: BACKGROUND
  Premature cardiovascular disease limits the duration and quality of life on long-term hemodialysis. The objective of this study was to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, using adjudicated data collected during the EValuation of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial.
  
  
  RESULTS
  EVOLVE was a randomized, double-blind, placebo-controlled clinical trial that randomized 3883 hemodialysis patients with moderate to severe secondary hyperparathyroidism to cinacalcet or matched placebo for up to 64 months. For this post hoc analysis, the outcome measure was fatal and nonfatal cardiovascular events reflecting atherosclerotic and nonatherosclerotic cardiovascular diseases. During the trial, 1518 patients experienced an adjudicated cardiovascular event, including 958 attributable to nonatherosclerotic disease. Of 1421 deaths during the trial, 768 (54%) were due to cardiovascular disease. Sudden death was the most frequent fatal cardiovascular event, accounting for 24.5% of overall mortality. Combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events (adjusted relative hazard 0.84, 95% CI 0.74 to 0.96), while the effect of cinacalcet on atherosclerotic events did not reach statistical significance.
  
  
  CONCLUSIONS
  Accepting the limitations of post hoc analysis, any benefits of cinacalcet on cardiovascular disease in the context of hemodialysis may result from attenuation of nonatherosclerotic processes.
  
  
  BACKGROUND
  Unique identifier: NCT00345839. URL: ClinicalTrials.gov.
authors.affiliation: University College London, London, UK (D.C.W.).
authors.forename: David C
authors.initials: DC
authors.lastname: Wheeler
authors.affiliation: Hôpital Manhès, Paris, France (G.M.L.).
authors.forename: Gerard M
authors.initials: GM
authors.lastname: London
authors.affiliation: Health Sciences Center St. John's, Newfoundland, Canada (P.S.P.).
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Parfrey
authors.affiliation: Denver Nephrology, Denver, CO (G.A.B.).
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Block
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.R.).
authors.forename: Ricardo
authors.initials: R
authors.lastname: Correa-Rotter
authors.affiliation: Amgen, Inc, Thousand Oaks, CA (B.D., Y.K., W.G.G., M.L.T.).
authors.forename: Bastian
authors.initials: B
authors.lastname: Dehmel
authors.affiliation: Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.).
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drüeke
authors.affiliation: Universitätsklinikum der RWTH Aachen, Aachen, Germany (F.).
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: Amgen, Inc, Thousand Oaks, CA (B.D., Y.K., W.G.G., M.L.T.).
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kubo
authors.affiliation: Stanford University School of Medicine, Palo Alto, CA (K.W.M., S.A., G.M.C.).
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Amgen, Inc, Thousand Oaks, CA (B.D., Y.K., W.G.G., M.L.T.).
authors.forename: William G
authors.initials: WG
authors.lastname: Goodman
authors.affiliation: Indiana University School of Medicine, Roudebush Veterans Administration Medical Center, Indianapolis, IN (S.M.M.).
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.affiliation: Amgen, Inc, Thousand Oaks, CA (B.D., Y.K., W.G.G., M.L.T.).
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Trotman
authors.affiliation: Stanford University School of Medicine, Palo Alto, CA (K.W.M., S.A., G.M.C.).
authors.forename: Safa
authors.initials: S
authors.lastname: Abdalla
authors.affiliation: Stanford University School of Medicine, Palo Alto, CA (K.W.M., S.A., G.M.C.).
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
authors.affiliation: Hennepin County Medical Center, University of Minnesota, Minneapolis, MN (C.A.H.).
authors.forename: Charles A
authors.initials: CA
authors.lastname: Herzog
mesh_terms: D050197:Atherosclerosis / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D057966:Calcimimetic Agents / Q000627:therapeutic use*; D000069449:Cinacalcet; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D057194:Intention to Treat Analysis; D007676:Kidney Failure, Chronic / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D008297:Male; D009281:Naphthalenes / Q000627:therapeutic use*; D006435:Renal Dialysis / Q000009:adverse effects* / Q000401:mortality; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D057966:Calcimimetic Agents; D009281:Naphthalenes; D000069449:Cinacalcet
keywords: atherosclerosis; cardiovascular diseases; heart failure; kidney; sudden death