A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease

Marc A. Pfeffer, Emmanuel A. Burdmann, Chao Yin Chen, Mark E. Cooper, Dick De Zeeuw, Kai Uwe Eckardt, Jan M. Feyzi, Peter Ivanovich, Reshma Kewalramani, Andrew S. Levey, Eldrin F. Lewis, Janet B. McGill, John J V McMurray, Patrick Parfrey, Hans Henrik Parving, Giuseppe Remuzzi, Ajay K. Singh, Scott D. Solomon, Robert Toto

Research output: Contribution to journalArticle

1326 Citations (Scopus)

Abstract

BACKGROUND: Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately tested. METHODS: In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter. The primary end points were the composite outcomes of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease. RESULTS: Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo (hazard ratio for darbepoetin alfa vs. placebo, 1.05; 95% confidence interval [CI], 0.94 to 1.17; P = 0.41). Death or end-stage renal disease occurred in 652 patients assigned to darbe poetin alfa and 618 patients assigned to placebo (hazard ratio, 1.06; 95% CI, 0.95 to 1.19; P = 0.29). Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo (hazard ratio, 1.92; 95% CI, 1.38 to 2.68; P<0.001). Red-cell transfusions were administered to 297 patients assigned to darbepoetin alfa and 496 patients assigned to placebo (P<0.001). There was only a modest improvement in patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group. CONCLUSIONS: The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event) and was associated with an increased risk of stroke. For many persons involved in clinical decision making, this risk will outweigh the potential benefits. (ClinicalTrials.gov number, NCT00093015.)

Original languageEnglish (US)
Pages (from-to)2019-2032
Number of pages14
JournalNew England Journal of Medicine
Volume361
Issue number21
DOIs
StatePublished - Nov 19 2009

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Chronic Renal Insufficiency
Type 2 Diabetes Mellitus
Placebos
Anemia
Hemoglobins
Stroke
Darbepoetin alfa
Confidence Intervals
Chronic Kidney Failure
Kidney
Myocardial Ischemia
Fatigue
Dialysis
Hospitalization
Heart Failure

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Pfeffer, M. A., Burdmann, E. A., Chen, C. Y., Cooper, M. E., De Zeeuw, D., Eckardt, K. U., ... Toto, R. (2009). A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. New England Journal of Medicine, 361(21), 2019-2032. https://doi.org/10.1056/NEJMoa0907845

A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. / Pfeffer, Marc A.; Burdmann, Emmanuel A.; Chen, Chao Yin; Cooper, Mark E.; De Zeeuw, Dick; Eckardt, Kai Uwe; Feyzi, Jan M.; Ivanovich, Peter; Kewalramani, Reshma; Levey, Andrew S.; Lewis, Eldrin F.; McGill, Janet B.; McMurray, John J V; Parfrey, Patrick; Parving, Hans Henrik; Remuzzi, Giuseppe; Singh, Ajay K.; Solomon, Scott D.; Toto, Robert.

In: New England Journal of Medicine, Vol. 361, No. 21, 19.11.2009, p. 2019-2032.

Research output: Contribution to journalArticle

Pfeffer, MA, Burdmann, EA, Chen, CY, Cooper, ME, De Zeeuw, D, Eckardt, KU, Feyzi, JM, Ivanovich, P, Kewalramani, R, Levey, AS, Lewis, EF, McGill, JB, McMurray, JJV, Parfrey, P, Parving, HH, Remuzzi, G, Singh, AK, Solomon, SD & Toto, R 2009, 'A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease', New England Journal of Medicine, vol. 361, no. 21, pp. 2019-2032. https://doi.org/10.1056/NEJMoa0907845
Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, De Zeeuw D, Eckardt KU et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. New England Journal of Medicine. 2009 Nov 19;361(21):2019-2032. https://doi.org/10.1056/NEJMoa0907845
Pfeffer, Marc A. ; Burdmann, Emmanuel A. ; Chen, Chao Yin ; Cooper, Mark E. ; De Zeeuw, Dick ; Eckardt, Kai Uwe ; Feyzi, Jan M. ; Ivanovich, Peter ; Kewalramani, Reshma ; Levey, Andrew S. ; Lewis, Eldrin F. ; McGill, Janet B. ; McMurray, John J V ; Parfrey, Patrick ; Parving, Hans Henrik ; Remuzzi, Giuseppe ; Singh, Ajay K. ; Solomon, Scott D. ; Toto, Robert. / A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. In: New England Journal of Medicine. 2009 ; Vol. 361, No. 21. pp. 2019-2032.
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abstract = "BACKGROUND: Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately tested. METHODS: In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter. The primary end points were the composite outcomes of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease. RESULTS: Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo (hazard ratio for darbepoetin alfa vs. placebo, 1.05; 95{\%} confidence interval [CI], 0.94 to 1.17; P = 0.41). Death or end-stage renal disease occurred in 652 patients assigned to darbe poetin alfa and 618 patients assigned to placebo (hazard ratio, 1.06; 95{\%} CI, 0.95 to 1.19; P = 0.29). Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo (hazard ratio, 1.92; 95{\%} CI, 1.38 to 2.68; P<0.001). Red-cell transfusions were administered to 297 patients assigned to darbepoetin alfa and 496 patients assigned to placebo (P<0.001). There was only a modest improvement in patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group. CONCLUSIONS: The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event) and was associated with an increased risk of stroke. For many persons involved in clinical decision making, this risk will outweigh the potential benefits. (ClinicalTrials.gov number, NCT00093015.)",
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T1 - A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease

AU - Pfeffer, Marc A.

AU - Burdmann, Emmanuel A.

AU - Chen, Chao Yin

AU - Cooper, Mark E.

AU - De Zeeuw, Dick

AU - Eckardt, Kai Uwe

AU - Feyzi, Jan M.

AU - Ivanovich, Peter

AU - Kewalramani, Reshma

AU - Levey, Andrew S.

AU - Lewis, Eldrin F.

AU - McGill, Janet B.

AU - McMurray, John J V

AU - Parfrey, Patrick

AU - Parving, Hans Henrik

AU - Remuzzi, Giuseppe

AU - Singh, Ajay K.

AU - Solomon, Scott D.

AU - Toto, Robert

PY - 2009/11/19

Y1 - 2009/11/19

N2 - BACKGROUND: Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately tested. METHODS: In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter. The primary end points were the composite outcomes of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease. RESULTS: Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo (hazard ratio for darbepoetin alfa vs. placebo, 1.05; 95% confidence interval [CI], 0.94 to 1.17; P = 0.41). Death or end-stage renal disease occurred in 652 patients assigned to darbe poetin alfa and 618 patients assigned to placebo (hazard ratio, 1.06; 95% CI, 0.95 to 1.19; P = 0.29). Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo (hazard ratio, 1.92; 95% CI, 1.38 to 2.68; P<0.001). Red-cell transfusions were administered to 297 patients assigned to darbepoetin alfa and 496 patients assigned to placebo (P<0.001). There was only a modest improvement in patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group. CONCLUSIONS: The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event) and was associated with an increased risk of stroke. For many persons involved in clinical decision making, this risk will outweigh the potential benefits. (ClinicalTrials.gov number, NCT00093015.)

AB - BACKGROUND: Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately tested. METHODS: In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter. The primary end points were the composite outcomes of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease. RESULTS: Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo (hazard ratio for darbepoetin alfa vs. placebo, 1.05; 95% confidence interval [CI], 0.94 to 1.17; P = 0.41). Death or end-stage renal disease occurred in 652 patients assigned to darbe poetin alfa and 618 patients assigned to placebo (hazard ratio, 1.06; 95% CI, 0.95 to 1.19; P = 0.29). Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo (hazard ratio, 1.92; 95% CI, 1.38 to 2.68; P<0.001). Red-cell transfusions were administered to 297 patients assigned to darbepoetin alfa and 496 patients assigned to placebo (P<0.001). There was only a modest improvement in patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group. CONCLUSIONS: The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event) and was associated with an increased risk of stroke. For many persons involved in clinical decision making, this risk will outweigh the potential benefits. (ClinicalTrials.gov number, NCT00093015.)

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