Critical Appraisal Topics Outline
Title: The use of Darbepoetin Alfa is not proven to have benefit in patients with
type 2 Diabetes and chronic kidney disease
Clinical bottom line:
The use of darbepoetin alfa in patients with diabetes and chronic kidney disease did not reduce
the risk of cardiovascular event and end-stage renal disease
Citation/s:
A trial of Darbepoetin Alfa in type 2 Diabetes and Chronic Kidney Disease
N Engl J Med. 2009 Nov 19;361(21):2019-32. Epub 2009 Oct 30.
Lead author's name and fax:
Marc A. Pfeffer, M.D., Ph.D., Emmanuel A. Burdmann, M.D., Ph.D., Chao-Yin Chen, Ph.D., et al
Clinical Scenario & PICO Question:
情境重點簡述：（與 PICO 有關的為主）
P: Patients with type 2 diabetes
I/E: Darbepoetin Alfa
C: Placebo
O: cardiovascular events, end-stage renal disease
Type of Question: therapy
Search Terms & Strategy:
Database: Pubmed
Key words & Search stratedy:
#4 Search #1 and #2 and #3
10:32:16
3
#3 Search (chronic kidney disease) AND (Therapy/Narrow[filter])
10:31:21
2348
#2 Search (type 2 diabetes) AND (Therapy/Narrow[filter])
10:30:58
5005
#1 Search (darbepoetin alfa) AND (Therapy/Narrow[filter])
10:30:10
84
The Study: Level of Evidence: 1b
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
The Evidence:
1.
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).
2.
Death or end-stage renal disease occurred in 652 patients assigned to darbepoetin alfa and 618 patients assigned to
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placebo (hazard ratio, 1.06; 95% CI, 0.95 to 1.19; P = 0.29).
3.
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).
Comments:
1.
The data may not be fully applicable to other patient populations. It is possible that other dosing strategies could be
developed to mitigate the risk of stroke while conserving the modest benefits of treatment.
2.
More extensive analyses of the patient-reported outcome measures are needed to assess the durability of the rather
modest improvement we observed only in the FACT-Fatigue score.
3.
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
4.
The use of darbepoetin alfa was associated with an increased risk of stroke. For many persons involved in clinical
decision making, this risk will outweigh the potential benefits.
References:
1.
Baseline characteristics in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).
Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, Ivanovich P, Kewalramani R, Levey
AS, Lewis EF, McGill J, McMurray JJ, Parfrey P, Parving HH, Remuzzi G, Singh AK, Solomon SD, Toto R, Uno H;
TREAT Investigators. Am J Kidney Dis. 2009 Jul;54(1):59-69. Epub 2009 Jun 5.
2.
Rationale--Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): evolving the management of
cardiovascular risk in patients with chronic kidney disease.
Mix TC, Brenner RM, Cooper ME, de Zeeuw D, Ivanovich P, Levey AS, McGill JB, McMurray JJ, Parfrey PS,
Parving HH, Pereira BJ, Remuzzi G, Singh AK, Solomon SD, Stehman-Breen C, Toto RD, Pfeffer MA. Am Heart J.
2005 Mar;149(3):408-13. Erratum in: Am Heart J. 2005 Jul;150(1):53.
Kill or Update By: 12/31/2010
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科部會議名稱：一般內科 EBM 個案討論會
舉行日期時間：12/23/2009, 0730-0830
報告者：姓名：R3 詹博強
指導臨床教師：黃俊雄
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Code: 128227
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Email: 128227@cch.org.tw