Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial

Patrick H. Pun, Safa Abdalla, Geoffrey A. Block, Glenn M. Chertow, Ricardo Correa-Rotter, Bastian Dehmel, Tilman B. Drüeke, Jürgen Floege, William G. Goodman, Charles A. Herzog, Gerard M. London, Kenneth W. Mahaffey, Sharon Moe, Patrick S. Parfrey, David C. Wheeler, John P. Middleton

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)421-431
Number of pages11
JournalHemodialysis International
Volume20
Issue number3
DOIs
StatePublished - Jul 1 2016

Fingerprint

Dialysis Solutions
Calcium
Cinacalcet Hydrochloride
Prescriptions
Renal Dialysis
Latin America
Sudden Cardiac Death
Unstable Angina
North America
Sudden Death
Parathyroid Hormone
Serum

Keywords

  • Cardiovascular
  • dialysate fluid compatibility and quality
  • international dialysis issues
  • outcomes research

ASJC Scopus subject areas

  • Hematology
  • Nephrology

Cite this

Pun, P. H., Abdalla, S., Block, G. A., Chertow, G. M., Correa-Rotter, R., Dehmel, B., ... Middleton, J. P. (2016). Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial. Hemodialysis International, 20(3), 421-431. https://doi.org/10.1111/hdi.12382

Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial. / Pun, Patrick H.; Abdalla, Safa; Block, Geoffrey A.; Chertow, Glenn M.; Correa-Rotter, Ricardo; Dehmel, Bastian; Drüeke, Tilman B.; Floege, Jürgen; Goodman, William G.; Herzog, Charles A.; London, Gerard M.; Mahaffey, Kenneth W.; Moe, Sharon; Parfrey, Patrick S.; Wheeler, David C.; Middleton, John P.

In: Hemodialysis International, Vol. 20, No. 3, 01.07.2016, p. 421-431.

Research output: Contribution to journalArticle

Pun, PH, Abdalla, S, Block, GA, Chertow, GM, Correa-Rotter, R, Dehmel, B, Drüeke, TB, Floege, J, Goodman, WG, Herzog, CA, London, GM, Mahaffey, KW, Moe, S, Parfrey, PS, Wheeler, DC & Middleton, JP 2016, 'Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial', Hemodialysis International, vol. 20, no. 3, pp. 421-431. https://doi.org/10.1111/hdi.12382
Pun PH, Abdalla S, Block GA, Chertow GM, Correa-Rotter R, Dehmel B et al. Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial. Hemodialysis International. 2016 Jul 1;20(3):421-431. https://doi.org/10.1111/hdi.12382
Pun, Patrick H. ; Abdalla, Safa ; Block, Geoffrey A. ; Chertow, Glenn M. ; Correa-Rotter, Ricardo ; Dehmel, Bastian ; Drüeke, Tilman B. ; Floege, Jürgen ; Goodman, William G. ; Herzog, Charles A. ; London, Gerard M. ; Mahaffey, Kenneth W. ; Moe, Sharon ; Parfrey, Patrick S. ; Wheeler, David C. ; Middleton, John P. / Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial. In: Hemodialysis International. 2016 ; Vol. 20, No. 3. pp. 421-431.
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