Anemia is a common and often debilitating complication of kidney disease that has been linked to poor quality of life and increased risk of hospitalization and death. The study, published in the March 3, 2010, issue of the Journal of the American Medical Association, addresses an ongoing controversy about the optimal management of anemia in dialysis patients. Although the condition can be successfully treated with ESAs and iron, several clinical studies have shown that correction of anemia may increase the risk of heart attack, heart failure, stroke or blood clots.
ESAs are forms of the human protein erythropoietin and work by stimulating the bone marrow to produce red blood cells. They are approved by the U.S. Food and Drug Administration (FDA) for treating anemia resulting from chronic kidney failure, chemotherapy and certain HIV treatments. The agents can also help to reduce the number of blood transfusions needed during and after certain major surgeries. The FDA approved the first ESA for use in the U.S. in 1989, but issued a public health advisory and added a black box warning to the product’s prescribing information in 2007, warning of increased risks of adverse events that were observed in earlier clinical studies.
Authors of the new research, led by M. Alan Brookhart, Ph.D., associate professor of epidemiology at the UNC Gillings School of Global Public Health, studied nearly 270,000 Medicare patients treated at U.S. dialysis centers. The researchers examined how individual dialysis center’s use of ESAs and iron affected mortality risk among patients.
“Dialysis units that managed severe anemia more aggressively with ESAs and intravenous iron had a one-year mortality rate that was 5 percent lower than more conservative dialysis units,” Brookhart said. “However, in cases of mild anemia, more intensive management of the condition was associated with a 10 percent increase in the rate of mortality.”
The new findings were based on observation rather than on a controlled clinical study, Brookhart noted.
“The randomized controlled trials of these drugs have suggested that there are risks associated with full correction of anemia in selected patients with kidney disease,” he said. “Our study suggests that similar risks may exist in the larger population of dialysis patients.”
The new study also builds on the earlier trial results with its suggestion that ESAs and iron, used appropriately, may lower the risk of death in patients with severe anemia. “It’s important that we continue studying the use of these drugs to better understand how we can maximize benefit and minimize harm,” Brookhart said.
Other study authors included Wolfgang C. Winkelmayer, M.D., associate professor of nephrology at Stanford University School of Medicine; Sebastian Schneeweiss, M.D., associate professor of medicine, and Jerry Avorn, M.D., professor of medicine, both from Harvard Medical School; Jun Liu, M.D., and Brian Bradbury, D.Sc., director of epidemiology in the nephrology therapeutic area at Amgen Inc.
ESAs used to treat the anemia of chronic kidney disease are marketed in the U.S. as Epogen (epoetin alpha) and Aranesp (darbepoetin alpha), with both being manufactured and marketed by Amgen. There are several formulations of intravenous iron available on the U.S. market.
The study was funded through an investigator-initiated contract from Amgen to the Brigham and Women’s Hospital. The research contract gave the compa