Controversial Anemia Drug Doesn't Cut Need for Transfusions
WEDNESDAY Sept. 5, 2007 -- A drug widely used to treat anemia does not reduce the need for blood transfusions among critically ill patients, but it may reduce mortality in trauma patients.
The drug, epoetin alfa (brand names Epogen and Procrit) has been under regulatory scrutiny because of potentially dangerous side effects.
"Unlike prior studies, this trial found that we didn't reduce blood transfusions, although it still increased hemoglobin levels," said study author Dr. Howard L. Corwin, a professor of medicine and anesthesiology at Dartmouth-Hitchcock Medical Center in Lebanon, N.H. "What we did find, particularly in trauma patients, was a reduction in mortality."
And this mortality benefit was likely due to other mechanisms of action caused by the drug. Once these mechanisms are understood, a whole new range of uses for the drug might be possible, the study authors said.
Overall, however, the drug did not seem to show an overwhelming benefit. "It didn't decrease the need for transfusions, which was the primary endpoint. And, in the majority of patients, which would be medical and surgical non-trauma patients, it did not improve survival," said Dr. Christian Cable, assistant professor of internal medicine at Texas A&M Health Science Center College of Medicine.
The study findings are published in the Sept. 6 issue of the New England Journal of Medicine.
Critically ill patients often develop anemia -- a decrease in the number of healthy red blood cells -- and require blood transfusions. But transfusions involve considerable risks, including death.
"It turns out that for most of the reasons transfusions are given, other than active bleeding, there is little evidence that they actually help and there is good evidence that red-blood-cell transfusions are associated with worse clinical outcomes," Corwin said.
The study authors hypothesized that giving epoetin alfa would reduce the need for transfusions. Epoetin alfa is a genetically engineered version of a natural protein, erythropoietin, which stimulates the bone marrow to make blood cells.
In May, a U.S. Food and Drug Administration advisory panel called for new warnings and additional safety studies on epoetin alfa and other anemia drugs, largely due to dangerous side effects such as the risk of blood clots, strokes, heart attacks and death.
In March, the FDA issued stronger label warnings for the popular drugs, which are also used for patients with chronic kidney failure and cancer.
And on Sept. 11, an FDA advisory panel is scheduled to meet to discuss new evidence on the safety of the drugs, although the panel will be looking at a different group of patients than those involved in this latest study.
For the study, the researchers enrolled 1,460 medical, surgical or trauma patients from 48 to 96 hours after admission to the intensive care unit. Each patient received either epoetin alfa or a placebo weekly for a maximum of three weeks, and all patients were followed for 140 days.
There was no difference in the number of patients who received a transfusion in the placebo or epoetin alfa group, or the number of red-cell units transfused, probably a result of changes in transfusion practice, Corwin said.
Side effects in general were comparable between the two groups, although clotting was higher in the epoetin alfa group. "That shouldn't be forgotten," Corwin said.
However, the concentration of hemoglobin, a protein in red blood cells that carries oxygen to tissues, did increase more in the epoetin alfa group than in the placebo group.
In addition, the mortality rate in patients receiving epoetin alfa was lower than among those receiving a placebo. That effect was most pronounced in trauma patients. "More research is needed to look at the trauma patients and the mechanism for epoetin alfa effect on mortality," Corwin said.
The beneficial mechanism appears to be something other than the drug's ability to enhance red blood cell formation.
"There's some data in animal studies and small clinical studies suggesting that epoetin alfa has a lot of other effects in addition to making blood cells, and we think it's one of these other mechanisms that is causing the mortality benefit," Corwin said.
"There is a whole range of other areas where epoetin alfa may have potential benefits through these other mechanisms," he continued. "This opens up a whole new area of study. There may be benefits in terms of function after strokes or head injury. There needs to be additional work to sort out the mechanisms responsible for this benefit."
To learn more about these anemia drugs, visit the U.S. Food and Drug Administration.
Posted: September 2007
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