Abstract | BACKGROUND: METHODS: RESULTS: Patients who had a poor initial response to darbepoetin alfa had a lower average hemoglobin level at 12 weeks and during follow-up than did patients with a better hemoglobin response (a change in hemoglobin level ranging from 2 to 15% or more) (P<0.001 for both comparisons), despite receiving higher doses of darbepoetin alfa (median dose, 232 μg vs. 167 μg; P<0.001). Patients with a poor response, as compared with those with a better response, had higher rates of the composite cardiovascular end point (adjusted hazard ratio, 1.31; 95% confidence interval [CI], 1.09 to 1.59) or death (adjusted hazard ratio, 1.41; 95% CI, 1.12 to 1.78). CONCLUSIONS: A poor initial hematopoietic response to darbepoetin alfa was associated with an increased subsequent risk of death or cardiovascular events as doses were escalated to meet target hemoglobin levels. Although the mechanism of this differential effect is not known, these findings raise concern about current target-based strategies for treating anemia in patients with chronic kidney disease. (Funded by Amgen; ClinicalTrials.gov number, NCT00093015.)
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Authors | Scott D Solomon, Hajime Uno, Eldrin F Lewis, Kai-Uwe Eckardt, Julie Lin, Emmanuel A Burdmann, Dick de Zeeuw, Peter Ivanovich, Andrew S Levey, Patrick Parfrey, Giuseppe Remuzzi, Ajay K Singh, Robert Toto, Fannie Huang, Jerome Rossert, John J V McMurray, Marc A Pfeffer, Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) Investigators |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 363
Issue 12
Pg. 1146-55
(Sep 16 2010)
ISSN: 1533-4406 [Electronic] United States |
PMID | 20843249
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Hematinics
- Hemoglobins
- Erythropoietin
- Darbepoetin alfa
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Topics |
- Aged
- Anemia
(drug therapy, etiology)
- Cardiovascular Diseases
(epidemiology, prevention & control)
- Chi-Square Distribution
- Darbepoetin alfa
- Diabetes Mellitus, Type 2
(blood, complications, mortality)
- Double-Blind Method
- Erythropoietin
(analogs & derivatives, therapeutic use)
- Female
- Hematinics
(therapeutic use)
- Hemoglobins
(metabolism)
- Humans
- Injections, Subcutaneous
- Kidney Failure, Chronic
(blood, complications, mortality)
- Male
- Middle Aged
- Proportional Hazards Models
- Risk
- Stroke
(epidemiology)
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