Effects of cinacalcet on fracture events in patients receiving hemodialysis: The EVOLVE trial

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

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%-29%.

Original languageEnglish
Pages (from-to)1466-1475
Number of pages10
JournalJournal of the American Society of Nephrology
Volume26
Issue number6
DOIs
StatePublished - Jun 1 2015

Fingerprint

Renal Dialysis
Placebos
Confidence Intervals
Intention to Treat Analysis
Cinacalcet Hydrochloride
Parathyroidectomy
Secondary Hyperparathyroidism
Pharmaceutical Preparations
Randomized Controlled Trials
Transplants
Mortality

ASJC Scopus subject areas

  • Nephrology

Cite this

Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators (2015). Effects of cinacalcet on fracture events in patients receiving hemodialysis: The EVOLVE trial. Journal of the American Society of Nephrology, 26(6), 1466-1475. https://doi.org/10.1681/ASN.2014040414

Effects of cinacalcet on fracture events in patients receiving hemodialysis : The EVOLVE trial. / Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators.

In: Journal of the American Society of Nephrology, Vol. 26, No. 6, 01.06.2015, p. 1466-1475.

Research output: Contribution to journalArticle

Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators 2015, 'Effects of cinacalcet on fracture events in patients receiving hemodialysis: The EVOLVE trial', Journal of the American Society of Nephrology, vol. 26, no. 6, pp. 1466-1475. https://doi.org/10.1681/ASN.2014040414
Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators. Effects of cinacalcet on fracture events in patients receiving hemodialysis: The EVOLVE trial. Journal of the American Society of Nephrology. 2015 Jun 1;26(6):1466-1475. https://doi.org/10.1681/ASN.2014040414
Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators. / Effects of cinacalcet on fracture events in patients receiving hemodialysis : The EVOLVE trial. In: Journal of the American Society of Nephrology. 2015 ; Vol. 26, No. 6. pp. 1466-1475.
@article{7323b451f44a44e6bc3d478140cb837e,
title = "Effects of cinacalcet on fracture events in patients receiving hemodialysis: The EVOLVE trial",
abstract = "Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2{\%}) patients randomized to placebo and 238 of 1948 (12.2{\%}) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95{\%} confidence interval [95{\%} CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95{\%} CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95{\%} CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95{\%} CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16{\%}-29{\%}.",
author = "{Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators} and Sharon Moe and Safa Abdalla and Chertow, {Glenn M.} and Parfrey, {Patrick S.} and Block, {Geoffrey A.} and Ricardo Correa-Rotter and J{\"u}rgen Floege and Herzog, {Charles A.} and London, {Gerard M.} and Mahaffey, {Kenneth W.} and Wheeler, {David C.} and Bastian Dehmel and Goodman, {William G.} and Dr{\"u}eke, {Tilman B.}",
year = "2015",
month = "6",
day = "1",
doi = "10.1681/ASN.2014040414",
language = "English",
volume = "26",
pages = "1466--1475",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "6",

}

TY - JOUR

T1 - Effects of cinacalcet on fracture events in patients receiving hemodialysis

T2 - The EVOLVE trial

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

AU - Moe, Sharon

AU - Abdalla, Safa

AU - Chertow, Glenn M.

AU - Parfrey, Patrick S.

AU - Block, Geoffrey A.

AU - Correa-Rotter, Ricardo

AU - Floege, Jürgen

AU - Herzog, Charles A.

AU - London, Gerard M.

AU - Mahaffey, Kenneth W.

AU - Wheeler, David C.

AU - Dehmel, Bastian

AU - Goodman, William G.

AU - Drüeke, Tilman B.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%-29%.

AB - Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%-29%.

UR - http://www.scopus.com/inward/record.url?scp=84930442261&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930442261&partnerID=8YFLogxK

U2 - 10.1681/ASN.2014040414

DO - 10.1681/ASN.2014040414

M3 - Article

C2 - 25505257

AN - SCOPUS:84930442261

VL - 26

SP - 1466

EP - 1475

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 6

ER -