Treatment of Anemia With Darbepoetin Prior to Dialysis Initiation and Clinical Outcomes: Analyses From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)

Finnian R. Mc Causland, Brian Claggett, Emmanuel A. Burdmann, Glenn M. Chertow, Mark E. Cooper, Kai Uwe Eckardt, Peter Ivanovich, 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 D Toto, Marc A. Pfeffer

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Rationale & Objective: Evidence from clinical trials to guide patient preparation for maintenance dialysis therapy is limited. Although anemia is associated with mortality and cardiovascular (CV) disease in individuals initiating maintenance dialysis therapy, it is not known if treatment of anemia before dialysis therapy initiation with erythropoiesis-stimulating agents alters outcomes. Study Design: Post hoc analysis of a randomized controlled trial. Setting & Participants: Participants with type 2 diabetes and chronic kidney disease who progressed to dialysis therapy (n = 590) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Exposure: Randomized treatment assignment (darbepoetin vs placebo). Outcomes: All-cause mortality, CV mortality, nonfatal myocardial infarction, heart failure, and stroke within the first 180 days of dialysis therapy initiation. Analytical Approach: Proportional hazards regression. Results: Overall, 590 of 4,038 (14.6%) participants initiated dialysis therapy during the trial (n = 298 and 292 in the darbepoetin and placebo groups, respectively). Corresponding hemoglobin levels were 11.3 ± 1.6 and 9.5 ± 1.5 g/dL (P < 0.001). Death from any cause occurred in 31 (10.4%) participants assigned to darbepoetin and 28 (9.6%) assigned to placebo (HR, 1.16; 95% CI, 0.69-1.93), while death from CV causes occurred in 15 (5.0%) and 13 (4.5%) participants, respectively (HR, 1.21; 95% CI, 0.58-1.93). There were no differences in risk for nonfatal myocardial infarction or heart failure. Stroke occurred in 8 (2.8%) participants assigned to darbepoetin and 1 (0.3%) assigned to placebo (HR, 8.6; 95% CI, 1.1-68.7). Limitations: Post hoc analyses of a subgroup of study participants. Conclusions: Despite initiating dialysis therapy with a higher hemoglobin level, prior treatment with darbepoetin was not associated with a reduction in mortality, myocardial infarction, or heart failure in the first 180 days, but a higher frequency of stroke was observed. In the absence of more definitive data, this may inform decisions regarding the use of erythropoiesis-stimulating agents to treat mild to moderate anemia in patients with type 2 diabetes and chronic kidney disease nearing dialysis therapy initiation.

Original languageEnglish (US)
JournalAmerican Journal of Kidney Diseases
DOIs
StateAccepted/In press - Jan 1 2018

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Anemia
Dialysis
Heart Failure
Therapeutics
Placebos
Hematinics
Mortality
Stroke
Myocardial Infarction
Chronic Renal Insufficiency
Type 2 Diabetes Mellitus
Darbepoetin alfa
Cause of Death
Hemoglobins
Maintenance
Cardiovascular Diseases
Randomized Controlled Trials
Clinical Trials

Keywords

  • Anemia
  • cardiovascular disease
  • chronic kidney disease (CKD)
  • darbepoetin
  • death
  • dialysis
  • dialysis initiation
  • erythropoiesis stimulating agent (ESA)
  • hemoglobin (Hb)
  • incident dialysis
  • stroke
  • transition to dialysis
  • type 2 diabetes mellitus (T2DM)

ASJC Scopus subject areas

  • Nephrology

Cite this

Treatment of Anemia With Darbepoetin Prior to Dialysis Initiation and Clinical Outcomes : Analyses From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). / Mc Causland, Finnian R.; Claggett, Brian; Burdmann, Emmanuel A.; Chertow, Glenn M.; Cooper, Mark E.; Eckardt, Kai Uwe; Ivanovich, Peter; 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 D; Pfeffer, Marc A.

In: American Journal of Kidney Diseases, 01.01.2018.

Research output: Contribution to journalArticle

Mc Causland, FR, Claggett, B, Burdmann, EA, Chertow, GM, Cooper, ME, Eckardt, KU, Ivanovich, P, Levey, AS, Lewis, EF, McGill, JB, McMurray, JJV, Parfrey, P, Parving, HH, Remuzzi, G, Singh, AK, Solomon, SD, Toto, RD & Pfeffer, MA 2018, 'Treatment of Anemia With Darbepoetin Prior to Dialysis Initiation and Clinical Outcomes: Analyses From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)', American Journal of Kidney Diseases. https://doi.org/10.1053/j.ajkd.2018.10.006
Mc Causland, Finnian R. ; Claggett, Brian ; Burdmann, Emmanuel A. ; Chertow, Glenn M. ; Cooper, Mark E. ; Eckardt, Kai Uwe ; Ivanovich, Peter ; 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 D ; Pfeffer, Marc A. / Treatment of Anemia With Darbepoetin Prior to Dialysis Initiation and Clinical Outcomes : Analyses From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). In: American Journal of Kidney Diseases. 2018.
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abstract = "Rationale & Objective: Evidence from clinical trials to guide patient preparation for maintenance dialysis therapy is limited. Although anemia is associated with mortality and cardiovascular (CV) disease in individuals initiating maintenance dialysis therapy, it is not known if treatment of anemia before dialysis therapy initiation with erythropoiesis-stimulating agents alters outcomes. Study Design: Post hoc analysis of a randomized controlled trial. Setting & Participants: Participants with type 2 diabetes and chronic kidney disease who progressed to dialysis therapy (n = 590) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Exposure: Randomized treatment assignment (darbepoetin vs placebo). Outcomes: All-cause mortality, CV mortality, nonfatal myocardial infarction, heart failure, and stroke within the first 180 days of dialysis therapy initiation. Analytical Approach: Proportional hazards regression. Results: Overall, 590 of 4,038 (14.6{\%}) participants initiated dialysis therapy during the trial (n = 298 and 292 in the darbepoetin and placebo groups, respectively). Corresponding hemoglobin levels were 11.3 ± 1.6 and 9.5 ± 1.5 g/dL (P < 0.001). Death from any cause occurred in 31 (10.4{\%}) participants assigned to darbepoetin and 28 (9.6{\%}) assigned to placebo (HR, 1.16; 95{\%} CI, 0.69-1.93), while death from CV causes occurred in 15 (5.0{\%}) and 13 (4.5{\%}) participants, respectively (HR, 1.21; 95{\%} CI, 0.58-1.93). There were no differences in risk for nonfatal myocardial infarction or heart failure. Stroke occurred in 8 (2.8{\%}) participants assigned to darbepoetin and 1 (0.3{\%}) assigned to placebo (HR, 8.6; 95{\%} CI, 1.1-68.7). Limitations: Post hoc analyses of a subgroup of study participants. Conclusions: Despite initiating dialysis therapy with a higher hemoglobin level, prior treatment with darbepoetin was not associated with a reduction in mortality, myocardial infarction, or heart failure in the first 180 days, but a higher frequency of stroke was observed. In the absence of more definitive data, this may inform decisions regarding the use of erythropoiesis-stimulating agents to treat mild to moderate anemia in patients with type 2 diabetes and chronic kidney disease nearing dialysis therapy initiation.",
keywords = "Anemia, cardiovascular disease, chronic kidney disease (CKD), darbepoetin, death, dialysis, dialysis initiation, erythropoiesis stimulating agent (ESA), hemoglobin (Hb), incident dialysis, stroke, transition to dialysis, type 2 diabetes mellitus (T2DM)",
author = "{Mc Causland}, {Finnian R.} and Brian Claggett and Burdmann, {Emmanuel A.} and Chertow, {Glenn M.} and Cooper, {Mark E.} and Eckardt, {Kai Uwe} and Peter Ivanovich and Levey, {Andrew S.} and Lewis, {Eldrin F.} and McGill, {Janet B.} and McMurray, {John J.V.} and Patrick Parfrey and Parving, {Hans Henrik} and Giuseppe Remuzzi and Singh, {Ajay K.} and Solomon, {Scott D.} and Toto, {Robert D} and Pfeffer, {Marc A.}",
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TY - JOUR

T1 - Treatment of Anemia With Darbepoetin Prior to Dialysis Initiation and Clinical Outcomes

T2 - Analyses From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)

AU - Mc Causland, Finnian R.

AU - Claggett, Brian

AU - Burdmann, Emmanuel A.

AU - Chertow, Glenn M.

AU - Cooper, Mark E.

AU - Eckardt, Kai Uwe

AU - Ivanovich, Peter

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 D

AU - Pfeffer, Marc A.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Rationale & Objective: Evidence from clinical trials to guide patient preparation for maintenance dialysis therapy is limited. Although anemia is associated with mortality and cardiovascular (CV) disease in individuals initiating maintenance dialysis therapy, it is not known if treatment of anemia before dialysis therapy initiation with erythropoiesis-stimulating agents alters outcomes. Study Design: Post hoc analysis of a randomized controlled trial. Setting & Participants: Participants with type 2 diabetes and chronic kidney disease who progressed to dialysis therapy (n = 590) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Exposure: Randomized treatment assignment (darbepoetin vs placebo). Outcomes: All-cause mortality, CV mortality, nonfatal myocardial infarction, heart failure, and stroke within the first 180 days of dialysis therapy initiation. Analytical Approach: Proportional hazards regression. Results: Overall, 590 of 4,038 (14.6%) participants initiated dialysis therapy during the trial (n = 298 and 292 in the darbepoetin and placebo groups, respectively). Corresponding hemoglobin levels were 11.3 ± 1.6 and 9.5 ± 1.5 g/dL (P < 0.001). Death from any cause occurred in 31 (10.4%) participants assigned to darbepoetin and 28 (9.6%) assigned to placebo (HR, 1.16; 95% CI, 0.69-1.93), while death from CV causes occurred in 15 (5.0%) and 13 (4.5%) participants, respectively (HR, 1.21; 95% CI, 0.58-1.93). There were no differences in risk for nonfatal myocardial infarction or heart failure. Stroke occurred in 8 (2.8%) participants assigned to darbepoetin and 1 (0.3%) assigned to placebo (HR, 8.6; 95% CI, 1.1-68.7). Limitations: Post hoc analyses of a subgroup of study participants. Conclusions: Despite initiating dialysis therapy with a higher hemoglobin level, prior treatment with darbepoetin was not associated with a reduction in mortality, myocardial infarction, or heart failure in the first 180 days, but a higher frequency of stroke was observed. In the absence of more definitive data, this may inform decisions regarding the use of erythropoiesis-stimulating agents to treat mild to moderate anemia in patients with type 2 diabetes and chronic kidney disease nearing dialysis therapy initiation.

AB - Rationale & Objective: Evidence from clinical trials to guide patient preparation for maintenance dialysis therapy is limited. Although anemia is associated with mortality and cardiovascular (CV) disease in individuals initiating maintenance dialysis therapy, it is not known if treatment of anemia before dialysis therapy initiation with erythropoiesis-stimulating agents alters outcomes. Study Design: Post hoc analysis of a randomized controlled trial. Setting & Participants: Participants with type 2 diabetes and chronic kidney disease who progressed to dialysis therapy (n = 590) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Exposure: Randomized treatment assignment (darbepoetin vs placebo). Outcomes: All-cause mortality, CV mortality, nonfatal myocardial infarction, heart failure, and stroke within the first 180 days of dialysis therapy initiation. Analytical Approach: Proportional hazards regression. Results: Overall, 590 of 4,038 (14.6%) participants initiated dialysis therapy during the trial (n = 298 and 292 in the darbepoetin and placebo groups, respectively). Corresponding hemoglobin levels were 11.3 ± 1.6 and 9.5 ± 1.5 g/dL (P < 0.001). Death from any cause occurred in 31 (10.4%) participants assigned to darbepoetin and 28 (9.6%) assigned to placebo (HR, 1.16; 95% CI, 0.69-1.93), while death from CV causes occurred in 15 (5.0%) and 13 (4.5%) participants, respectively (HR, 1.21; 95% CI, 0.58-1.93). There were no differences in risk for nonfatal myocardial infarction or heart failure. Stroke occurred in 8 (2.8%) participants assigned to darbepoetin and 1 (0.3%) assigned to placebo (HR, 8.6; 95% CI, 1.1-68.7). Limitations: Post hoc analyses of a subgroup of study participants. Conclusions: Despite initiating dialysis therapy with a higher hemoglobin level, prior treatment with darbepoetin was not associated with a reduction in mortality, myocardial infarction, or heart failure in the first 180 days, but a higher frequency of stroke was observed. In the absence of more definitive data, this may inform decisions regarding the use of erythropoiesis-stimulating agents to treat mild to moderate anemia in patients with type 2 diabetes and chronic kidney disease nearing dialysis therapy initiation.

KW - Anemia

KW - cardiovascular disease

KW - chronic kidney disease (CKD)

KW - darbepoetin

KW - death

KW - dialysis

KW - dialysis initiation

KW - erythropoiesis stimulating agent (ESA)

KW - hemoglobin (Hb)

KW - incident dialysis

KW - stroke

KW - transition to dialysis

KW - type 2 diabetes mellitus (T2DM)

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