Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis

The evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial

Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators

Research output: Contribution to journalArticle

128 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)27-39
Number of pages13
JournalCirculation
Volume132
Issue number1
DOIs
StatePublished - Jan 1 2015

Fingerprint

Renal Dialysis
Cardiovascular Diseases
Confidence Intervals
Serum
Therapeutics
Mortality
Heart Failure
Placebos
Secondary Hyperparathyroidism
Sudden Cardiac Death
Kidney Diseases
fibroblast growth factor 23
Cinacalcet Hydrochloride
Parathyroid Hormone
Vitamin D
Minerals
Blood Vessels
Hospitalization
Randomized Controlled Trials
Phosphates

Keywords

  • arrhythmias, cardiac
  • calcium
  • death, sudden, cardiac
  • renal insufficiency, chronic
  • ventricular remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators. / Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis : The evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial. In: Circulation. 2015 ; Vol. 132, No. 1. pp. 27-39.
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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. 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.",
keywords = "arrhythmias, cardiac, calcium, death, sudden, cardiac, renal insufficiency, chronic, ventricular remodeling",
author = "{Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators} and Moe, {Sharon M.} and Chertow, {Glenn M.} and Parfrey, {Patrick S.} and Yumi Kubo and Block, {Geoffrey A.} and Ricardo Correa-Rotter and Dr{\"u}eke, {Tilman B.} and Herzog, {Charles A.} and London, {Gerard M.} and Mahaffey, {Kenneth W.} and Wheeler, {David C.} and Maria Stolina and Bastian Dehmel and Goodman, {William G.} and J{\"u}rgen Floege and J. Santos and {Najun Zarazaga}, C. and I. Marin and N. Garrote and A. Cusumano and N. Pe{\~n}alba and {Del Valle}, E. and L. Juncos and {Martinez Saye}, J. and L. Lef and V. Altobelli and G. Petraglia and {Rosa Diez}, G. and W. Douthat and J. Lobo and C. Gallart and A. Lafalla and G. Diez and B. Linares and N. Lopez and N. Ramirez and R. Gonzalez and R. Valtuille and H. Beresan and O. Hermida and G. Rudolf and N. Marchetta and M. Rano and M. Ramirez and N. Garc{\'i}a and A. Gillies and B. Jones and E. Pedagogos and Tuazon, {Jennifer A} and Daniel Batlle",
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Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis : The evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial. / Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators.

In: Circulation, Vol. 132, No. 1, 01.01.2015, p. 27-39.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis

T2 - The evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial

AU - Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators

AU - Moe, Sharon M.

AU - Chertow, Glenn M.

AU - Parfrey, Patrick S.

AU - Kubo, Yumi

AU - Block, Geoffrey A.

AU - Correa-Rotter, Ricardo

AU - Drüeke, Tilman B.

AU - Herzog, Charles A.

AU - London, Gerard M.

AU - Mahaffey, Kenneth W.

AU - Wheeler, David C.

AU - Stolina, Maria

AU - Dehmel, Bastian

AU - Goodman, William G.

AU - Floege, Jürgen

AU - Santos, J.

AU - Najun Zarazaga, C.

AU - Marin, I.

AU - Garrote, N.

AU - Cusumano, A.

AU - Peñalba, N.

AU - Del Valle, E.

AU - Juncos, L.

AU - Martinez Saye, J.

AU - Lef, L.

AU - Altobelli, V.

AU - Petraglia, G.

AU - Rosa Diez, G.

AU - Douthat, W.

AU - Lobo, J.

AU - Gallart, C.

AU - Lafalla, A.

AU - Diez, G.

AU - Linares, B.

AU - Lopez, N.

AU - Ramirez, N.

AU - Gonzalez, R.

AU - Valtuille, R.

AU - Beresan, H.

AU - Hermida, O.

AU - Rudolf, G.

AU - Marchetta, N.

AU - Rano, M.

AU - Ramirez, M.

AU - García, N.

AU - Gillies, A.

AU - Jones, B.

AU - Pedagogos, E.

AU - Tuazon, Jennifer A

AU - Batlle, Daniel

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

KW - arrhythmias, cardiac

KW - calcium

KW - death, sudden, cardiac

KW - renal insufficiency, chronic

KW - ventricular remodeling

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U2 - 10.1161/CIRCULATIONAHA.114.013876

DO - 10.1161/CIRCULATIONAHA.114.013876

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SP - 27

EP - 39

JO - Circulation

JF - Circulation

SN - 0009-7322

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