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. Methods and 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.

Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis: The evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial / Moe, S. M.; Chertow, G.; Parfrey, P.; Kubo, Y.; Block, G.; Correa-Rotter, R.; Drüeke, T. B.; Herzog, C.; London, G. M.; Mahaffey, K. W.; Wheeler, D. C.; Stolina, M.; Dehmel, B.; Goodman, W. G.; Floege, J.; Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial, Investigators; Cappelli, Gianni. - In: CIRCULATION. - ISSN 0009-7322. - 132:1(2015), pp. 27-39. [10.1161/CIRCULATIONAHA.114.013876]

Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis: The evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial

Cappelli, Gianni
Membro del Collaboration Group
2015

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. Methods and 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.
2015
9-giu-2015
132
1
27
39
Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis: The evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial / Moe, S. M.; Chertow, G.; Parfrey, P.; Kubo, Y.; Block, G.; Correa-Rotter, R.; Drüeke, T. B.; Herzog, C.; London, G. M.; Mahaffey, K. W.; Wheeler, D. C.; Stolina, M.; Dehmel, B.; Goodman, W. G.; Floege, J.; Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial, Investigators; Cappelli, Gianni. - In: CIRCULATION. - ISSN 0009-7322. - 132:1(2015), pp. 27-39. [10.1161/CIRCULATIONAHA.114.013876]
Moe, S. M.; Chertow, G.; Parfrey, P.; Kubo, Y.; Block, G.; Correa-Rotter, R.; Drüeke, T. B.; Herzog, C.; London, G. M.; Mahaffey, K. W.; Wheeler, D. C...espandi
File in questo prodotto:
File Dimensione Formato  
Cinacalcet__Circulation_2015.pdf

Open access

Descrizione: articolo
Tipologia: Versione pubblicata dall'editore
Dimensione 1.56 MB
Formato Adobe PDF
1.56 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1137630
Citazioni
  • ???jsp.display-item.citation.pmc??? 97
  • Scopus 254
  • ???jsp.display-item.citation.isi??? 233
social impact