September 6, 2007
Efficacy and Safety of Epoetin Alfa in Critically Ill Patients.
What was the research question?
Does the treatment with recombinant human erythropoietin (epoetin alfa) reduce the need for red-cell transfusions in critically ill patients?
How did they do it?
A prospective, randomized, placebo-controlled trial at 115 centers in the USA
1460 critically ill medical, surgical, or trauma patients between 48 and 96 hours and hemoglobin <12 g/dL, were randomized to receive weakly 40,000 U of Epoetin alfa for three weeks (733 patients) or placebo (727 patients).
Patients with history of acute ischemic heart disease, PE, DVT, or stroke were excluded.
RBC transfusion was left for the discretion of the treating team, but a target of 7-9 g/dL was recommended. EPO was held if Hg >12 g/dL.
The primary end point was the percentage of patients who received a red-cell transfusion.
Secondary end points included the number of red-cell units transfused, mortality, and the change in hemoglobin concentration from baseline.
What did they find?
Percentage of patients who received any RBC transfusion was not significantly different in the EPO group compared to placebo (46% vs. 48.3%, P=0.34).
Hg concentration was higher in the EPO group compared to the placebo group (1.6 g/dL vs. 1.2 g/dL, P<0.001).
29-day mortality tended to be lower in the EPO group but not significantly different (8.5% vs. 11.4%, HR 0.79; 95% CI, 0.56 to 1.10)
In the pre-specified trauma group, 29-day mortality was significantly better in the EPO group compared to the placebo group (3.5% vs. 6.6%, HR 0.37; 95% CI, 0.19 to 0.72, NNT 32). Same for the 180-day mortality (6% vs. 9.2%, HR 0.86; 95% CI, 0.65 to 1.13).
EPO was associated with a higher risk of thrombotic vascular events (16.5% vs 11.5%, HR 1.41; 95% CI, 1.06 to 1.86, P=0.008, NNH 21).
Are there any limitations?
Mortality was a secondary endpoint, and the study is not powered to confirm a beneficial effect.
Compared to EPO-1 and EPO-2 which showed a decrease RBC requirement, this study did not, but likely secondary to the change in the transfusion threshold in the ICU.
What does it mean?
Epoetin alfa did not reduce the number of RBC transfusion or mortality in general ICU patient and increased the incidence of thrombotic events. However, in a predefined trauma group, mortality was decreased.
No routine use of epoetin alfa is critically ill patients. More data is needed in traum patients.