title: Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial.
abstract: Among patients receiving hemodialysis, abnormalities in calcium regulation have been linked to an increased risk of cardiovascular events. Cinacalcet lowers serum calcium concentrations through its effect on parathyroid hormone secretion and has been hypothesized to reduce the risk of cardiovascular events. In observational cohort studies, prescriptions of low dialysate calcium concentration and larger observed serum-dialysate calcium gradients have been associated with higher risks of in-dialysis facility or peri-dialytic sudden cardiac arrest. We performed this study to examine the risks associated with dialysate calcium and serum-dialysate gradients among participants in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. In EVOLVE, 3883 hemodialysis patients were randomized 1:1 to cinacalcet or placebo. Dialysate calcium was administered at the discretion of treating physicians. We examined whether baseline dialysate calcium concentration or the serum-dialysate calcium gradient modified the effect of cinacalcet on the following adjudicated endpoints: (1) primary composite endpoint (death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure, or peripheral vascular event); (2) cardiovascular death; and (3) sudden death. In EVOLVE, use of higher dialysate calcium concentrations was more prevalent in Europe and Latin America compared with North America. There was a significant fall in serum calcium concentration in the cinacalcet group; dialysate calcium concentrations were changed infrequently in both groups. There was no association between baseline dialysate calcium concentration or serum-dialysate calcium gradient and the endpoints examined. Neither the baseline dialysate calcium nor the serum-dialysate calcium gradient significantly modified the effects of cinacalcet on the outcomes examined. The effects of cinacalcet on cardiovascular death and major cardiovascular events are not altered by the dialysate calcium prescription and serum-dialysate calcium gradient.
authors.affiliation: Department of Medicine, Duke University, Durham, North Carolina, USA.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Pun
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA.
authors.forename: Safa
authors.initials: S
authors.lastname: Abdalla
authors.affiliation: Denver Nephrology, Denver, Colorado, USA.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Block
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA.
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Chertow
authors.affiliation: Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, District Federal, Mexico.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Correa-Rotter
authors.affiliation: Amgen, Inc, Thousand Oaks, California, USA.
authors.forename: Bastian
authors.initials: B
authors.lastname: Dehmel
authors.affiliation: Inserm Unit 1088, UFR Médecine/Pharmacie, Université de Picardie, Amiens, France.
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drüeke
authors.affiliation: Department of Nephrology, Universitätsklinikum der RWTH Aachen, Aachen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: Amgen, Inc, Thousand Oaks, California, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Goodman
authors.affiliation: University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Herzog
authors.affiliation: Hôpital Manhès, Paris, France.|Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, USA.
authors.forename: Gerard M
authors.initials: GM
authors.lastname: London
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Hôpital Manhès, Paris, France.|Indiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, USA.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.affiliation: Health Sciences Center, St. John's, Newfoundland, Canada.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Parfrey
authors.affiliation: University College London, London, United Kingdom.
authors.forename: David C
authors.initials: DC
authors.lastname: Wheeler
authors.affiliation: Department of Medicine, Duke University, Durham, North Carolina, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Middleton
mesh_terms: D002318:Cardiovascular Diseases / Q000628:therapy*; D000069449:Cinacalcet / Q000627:therapeutic use*; D015314:Dialysis Solutions / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects
chemical_list: D015314:Dialysis Solutions; D000069449:Cinacalcet
keywords: Cardiovascular; dialysate fluid compatibility and quality; international dialysis issues; outcomes research