title: Cinacalcet, Fibroblast Growth Factor-23, and Cardiovascular Disease in Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial.
abstract: BACKGROUND
  Patients with kidney disease have disordered bone and mineral metabolism, including elevated serum concentrations of fibroblast growth factor-23 (FGF23). These elevated concentrations are associated with cardiovascular and all-cause mortality. The objective was to determine the effects of the calcimimetic cinacalcet (versus placebo) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events.
  
  
  RESULTS
  This was a secondary analysis of a randomized clinical trial comparing cinacalcet to placebo in addition to conventional therapy (phosphate binders/vitamin D) in patients receiving hemodialysis with secondary hyperparathyroidism (intact parathyroid hormone ≥300 pg/mL). The primary study end point was time to death or a first nonfatal cardiovascular event (myocardial infarction, hospitalization for angina, heart failure, or a peripheral vascular event). This analysis included 2985 patients (77% of randomized) with serum samples at baseline and 2602 patients (67%) with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% versus 28%) reductions in FGF23. Among patients randomized to cinacalcet, a ≥30% reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point (relative hazard, 0.82; 95% confidence interval, 0.69-0.98), cardiovascular mortality (relative hazard, 0.66; 95% confidence interval, 0.50-0.87), sudden cardiac death (relative hazard, 0.57; 95% confidence interval, 0.37-0.86), and heart failure (relative hazard, 0.69; 95% confidence interval, 0.48-0.99).
  
  
  CONCLUSIONS
  Treatment with cinacalcet significantly lowers serum FGF23. Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00345839.
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.). smoe@iupui.edu.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Parfrey
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kubo
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Block
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: Ricardo
authors.initials: R
authors.lastname: Correa-Rotter
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drüeke
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: Charles A
authors.initials: CA
authors.lastname: Herzog
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: Gerard M
authors.initials: GM
authors.lastname: London
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: David C
authors.initials: DC
authors.lastname: Wheeler
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: Maria
authors.initials: M
authors.lastname: Stolina
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: Bastian
authors.initials: B
authors.lastname: Dehmel
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: William G
authors.initials: WG
authors.lastname: Goodman
authors.affiliation: From Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis (S.M.M.); Stanford University School of Medicine, Palo Alto, CA (G.M.C., K.W.M.); Health Sciences Center, St. John's, NL, Canada (P.S.P.); Amgen Inc, Thousand Oaks, CA (Y.K., M.S., B.D., W.G.G.); Denver Nephrology, CO (G.A.B.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico (R.C.-R.); Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France (T.B.D.); University of Minnesota, Minneapolis (C.A.H.); Hôpital Manhès, Paris, France (G.M.L.); University College London, London, UK (D.C.W.); and Universitätsklinikum der RWTH Aachen, Germany (J.F.).
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality / Q000517:prevention & control*; D000069449:Cinacalcet; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D006980:Hyperthyroidism / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D006435:Renal Dialysis / Q000401:mortality
chemical_list: C000717427:FGF23 protein, human; D009281:Naphthalenes; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000069449:Cinacalcet
keywords: arrhythmias, cardiac; calcium; death, sudden, cardiac; renal insufficiency, chronic; ventricular remodeling