Improved survival of critically ill trauma patients treated with recombinant human erythropoietin.
BACKGROUND
A randomized, double-blind, placebo-controlled, multicenter trial (EPO-2, N = 1,302) in anemic critically ill patients demonstrated a 29-day survival benefit in the trauma subgroup receiving epoetin alfa (mortality 8.9% vs. 4.1%). A second similarly designed trial (EPO-3, N = 1,460) confirmed this survival benefit in the epoetin alfa-treated trauma cohort (mortality 6.7% vs. 3.5%). This analysis presents trauma cohort data from both trials for evaluation of the impact of baseline factors including trauma-specific variables on outcomes.


METHODS
Patients received 40,000 U epoetin alfa or placebo weekly, for a total of 4 (EPO-2) or 3 (EPO-3) doses, starting on ICU day 3. Kaplan-Meier survival curves for the two groups were compared using the log-rank test. Univariate and multivariate Cox proportional hazard regression methods were used to evaluate relationship between baseline factors and mortality.


RESULTS
Demographic and trauma variables at baseline were comparable. Mortality was consistently reduced by approximately 50% in both studies (EPO-2--day 29 unadjusted HR: 0.46, 95% CI: 0.24-0.89; EPO-3--day 29 unadjusted HR: 0.51, 95% CI: 0.27-0.98.). Adjusting for baseline and trauma variables had minimal effect on hazard ratios for mortality at day 29 (EPO-2--day 29 adjusted HR: 0.50, 95% CI: 0.26-0.97; EPO-3--day 29 adjusted HR: 0.38, 95% CI: 0.19-0.74) and day 140 (EPO-3--adjusted HR: 0.39, 95% CI: 0.21-0.72). In EPO-3, there appeared to be an increase in clinically relevant thrombovascular events in the epoetin alfa treated group (16.4% vs. 12.5%, RR: 1.3, 95% CI: 0.93-1.85) but not in EPO-2 (11.1% vs. 13.3%, RR: 0.84, 95% CI: 0.56-1.28).


CONCLUSIONS
Epoetin alfa demonstrated a survival advantage in both of the critically ill trauma patient cohorts of two prospective, randomized clinical trials, which was not affected by baseline factors including trauma-specific variables. A definitive study in trauma subjects is warranted.
Napolitano
Lena M
LM
Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0033, USA. lenan@umich.edu
Fabian
Timothy C
TC
Kelly
Kathleen M
KM
Bailey
Jeffrey A
JA
Block
Ernest F
EF
Langholff
Wayne
W
Enny
Christopher
C
Corwin
Howard L
HL
D001803:Blood Transfusion / Q000706:statistics & numerical data; D015897:Comorbidity; D016638:Critical Illness / Q000453:epidemiology / Q000401:mortality*; D004311:Double-Blind Method; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D014947:Wounds and Injuries / Q000453:epidemiology / Q000401:mortality*
D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa