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Previous Volume 357:965-976 September 6, 2007 Number 10 Next

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ABSTRACT

Background Anemia, which is common in the critically ill, is often treated with red-cell transfusions, which are associated with poor clinical outcomes. We hypothesized that therapy with recombinant human erythropoietin (epoetin alfa) might reduce the need for red-cell transfusions.

Methods In this prospective, randomized, placebo-controlled trial, we enrolled 1460 medical, surgical, or trauma patients between 48 and 96 hours after admission to the intensive care unit. Epoetin alfa (40,000 U) or placebo was administered weekly, for a maximum of 3 weeks; patients were followed for 140 days. The primary end point was the percentage of patients who received a red-cell transfusion. Secondary end points were the number of red-cell units transfused, mortality, and the change in hemoglobin concentration from baseline.

Results As compared with the use of placebo, epoetin alfa therapy did not result in a decrease in either the number of patients who received a red-cell transfusion (relative risk for the epoetin alfa group vs. the placebo group, 0.95; 95% confidence interval [CI], 0.85 to 1.06) or the mean (±SD) number of red-cell units transfused (4.5±4.6 units in the epoetin alfa group and 4.3±4.8 units in the placebo group, P=0.42). However, the hemoglobin concentration at day 29 increased more in the epoetin alfa group than in the placebo group (1.6±2.0 g per deciliter vs. 1.2±1.8 g per deciliter, P<0.001). Mortality tended to be lower at day 29 among patients receiving epoetin alfa (adjusted hazard ratio, 0.79; 95% CI, 0.56 to 1.10); this effect was also seen in prespecified analyses in those with a diagnosis of trauma (adjusted hazard ratio, 0.37; 95% CI, 0.19 to 0.72). A similar pattern was seen at day 140 (adjusted hazard ratio, 0.86; 95% CI, 0.65 to 1.13), particularly in those with trauma (adjusted hazard ratio, 0.40; 95% CI, 0.23 to 0.69). As compared with placebo, epoetin alfa was associated with a significant increase in the incidence of thrombotic events (hazard ratio, 1.41; 95% CI, 1.06 to 1.86).

Conclusions The use of epoetin alfa does not reduce the incidence of red-cell transfusion among critically ill patients, but it may reduce mortality in patients with trauma. Treatment with epoetin alfa is associated with an increase in the incidence of thrombotic events. (ClinicalTrials.gov number, NCT00091910 [ClinicalTrials.gov] .)

Source Information

From Dartmouth–Hitchcock Medical Center, Lebanon, NH (H.L.C., A.G.); University of Tennessee Health Science Center, Memphis (T.C.F.); Vanderbilt University Medical Center, Nashville (A.M.); Stanford University Medical Center, Stanford, CA (R.G.P.); University of Massachusetts Memorial Medical Center, Worcester (S.H.); Johnson & Johnson Pharmaceutical Research and Development, Raritan, NJ (R.A., P.J.B., P.B., M.A.K.); and Boston University School of Medicine, Boston, and BattelleCRO, Newton, MA (M.J.C.).

Address reprint requests to Dr. Howard Corwin at Dartmouth–Hitchcock Medical Center, 1 Medical Center Dr., Lebanon, NH 03756, or at howard.l.corwin{at}hitchcock.org.

Full Text of this Article

Related Letters:

Epoetin Alfa in Critically Ill Patients
Mikhail A., van der Putten K., Braam B., Gaillard C. A., Eisen L. A., Cooke C. R., Rubenfeld G. D., Corwin H. L.
Extract | Full Text | PDF  
N Engl J Med 2007; 357:2515-2517, Dec 13, 2007. Correspondence

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