Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis

The EVOLVE Trial Investigators

Research output: Contribution to journalArticle

535 Citations (Scopus)

Abstract

BACKGROUND: Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients. METHODS: In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle. RESULTS: The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P = 0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet. CONCLUSIONS: In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis.

Original languageEnglish (US)
Pages (from-to)2482-2494
Number of pages13
JournalNew England Journal of Medicine
Volume367
Issue number26
DOIs
StatePublished - Dec 27 2012

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Dialysis
Cardiovascular Diseases
Secondary Hyperparathyroidism
Placebos
Calcimimetic Agents
Vascular Calcification
Cinacalcet Hydrochloride
Intention to Treat Analysis
Hypocalcemia
Unstable Angina
Sterols
Parathyroid Hormone
Chronic Renal Insufficiency
Vitamin D
Minerals
Blood Vessels
Renal Dialysis
Hospitalization
Heart Failure
Phosphates

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. / The EVOLVE Trial Investigators.

In: New England Journal of Medicine, Vol. 367, No. 26, 27.12.2012, p. 2482-2494.

Research output: Contribution to journalArticle

The EVOLVE Trial Investigators. / Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. In: New England Journal of Medicine. 2012 ; Vol. 367, No. 26. pp. 2482-2494.
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abstract = "BACKGROUND: Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients. METHODS: In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle. RESULTS: The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2{\%}) in the cinacalcet group and 952 of 1935 patients (49.2{\%}) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95{\%} confidence interval, 0.85 to 1.02; P = 0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet. CONCLUSIONS: In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis.",
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T1 - Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis

AU - The EVOLVE Trial Investigators

AU - Block, G. A.

AU - Correa-Rotter, R.

AU - Drüeke, T. B.

AU - Floege, J.

AU - Goodman, W. G.

AU - Herzog, C. A.

AU - Kubo, Y.

AU - London, G. M.

AU - Mahaffey, K. W.

AU - Mix, T. C.

AU - Moe, S. M.

AU - Trotman, M. L.

AU - Wheeler, D. C.

AU - Parfrey, P. S.

AU - Chertow, G.

AU - Hennekens, C.

AU - Baigent, C.

AU - Brown, W.

AU - O'brien, P.

AU - Anderson, S.

AU - Hoel, J.

AU - Szczech, L.

AU - Patel, U.

AU - Wampole, J.

AU - Pun, P.

AU - Felker, M.

AU - Inrig, J.

AU - Shah, S.

AU - Hernandez, A.

AU - Patel, C.

AU - Brennan, M.

AU - Albizem, M.

AU - Capper, E.

AU - Cauchi, L.

AU - Cheng, S.

AU - Dehmel, B.

AU - Dhami, K.

AU - Durham, C.

AU - Francioni, M.

AU - Gadd, S.

AU - Goodman, B.

AU - Guimaraes, L.

AU - Grey, N.

AU - Hamlin, R.

AU - Harris, C.

AU - Harris, E.

AU - Heavey, S.

AU - Heiges, T.

AU - Heiser, D.

AU - Jaeger, P.

PY - 2012/12/27

Y1 - 2012/12/27

N2 - BACKGROUND: Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients. METHODS: In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle. RESULTS: The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P = 0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet. CONCLUSIONS: In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis.

AB - BACKGROUND: Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients. METHODS: In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle. RESULTS: The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P = 0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet. CONCLUSIONS: In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis.

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