A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease.
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 darbepoetin 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.)
Pfeffer
Marc A
MA
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. mpfeffer@rics.bwh.harvard.edu
Burdmann
Emmanuel A
EA
Chen
Chao-Yin
CY
Cooper
Mark E
ME
de Zeeuw
Dick
D
Eckardt
Kai-Uwe
KU
Feyzi
Jan M
JM
Ivanovich
Peter
P
Kewalramani
Reshma
R
Levey
Andrew S
AS
Lewis
Eldrin F
EF
McGill
Janet B
JB
McMurray
John J V
JJ
Parfrey
Patrick
P
Parving
Hans-Henrik
HH
Remuzzi
Giuseppe
G
Singh
Ajay K
AK
Solomon
Scott D
SD
Toto
Robert
R
D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control; D000068256:Darbepoetin alfa; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004311:Double-Blind Method; D004921:Erythropoietin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications*; D020521:Stroke / Q000139:chemically induced / Q000453:epidemiology
D006397:Hematinics; D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa