Study finds increased risks for potential deadly complications
WEDNESDAY, May 5 (HealthDay News) -- The powerful drugs used to fight anemia caused by kidney failure increase the risk for cardiovascular problems such as heart attack, a major study has found.
A meta-analysis of 27 trials, which included more than 10,000 people who were given the drugs, known as erythropoiesis-stimulating agents (ESAs), found that those who took the drugs at the highest dosages had a 51 percent increased risk for stroke and a 33 percent increased risk for thrombosis, or blockage of an artery. The study, by an international group of experts, was published online May 3 in Annals of Internal Medicine.
The increased risk for death (9 percent) and serious cardiovascular events such as heart attacks (15 percent) did not reach statistical significance, the analysis found.
The U.S. Food and Drug Administration has acted to control the use of ESAs marketed as Epogen, Procrit and Aranesp, which stimulate production of red blood cells to treat the anemia caused by kidney failure and cancer chemotherapy. The agency has added a "black box" warning of dangers to ESA labeling.
The new study adds emphasis to such moves, said Dr. Ajay K. Singh, an associate professor of medicine at Harvard Medical School and a nephrologist at Brigham and Women's Hospital in Boston.
"This meta-analysis shows increased risk with no benefit," Singh said. "The supposed benefit is that ESAs improve quality of life and make people feel better. This study suggests that these drugs, used at considerable cost, don't show any benefit in terms of those endpoints."
ESAs cost Medicare $2 billion a year, Singh said, making them the most expensive drugs in terms of cost that the government has paid for.
Yet ESAs do have a role in treating some people with chronic kidney disease, despite their dangers, Singh said.
The new FDA rules, put into effect earlier this year, require that Amgen, the company that markets the drugs, disseminate a guide informing cancer patients of the drugs' risks and that doctors discuss those risks with the patients and obtain signatures authorizing their use.
The FDA also requires certification and active, continuing enrollment in an educational program for all doctors prescribing ESAs to cancer patients.
The rules do not apply to people given ESAs for conditions other than cancer.
The decision to treat someone with chronic kidney disease with an ESA must be made patient by patient, Singh said. But one major factor is whether the patient requires dialysis, he said.
"Those who are on dialysis tend to have severe anemia," Singh said. "Those who are not on dialysis usually have anemia that is less severe."
Before an ESA is used, "you need to have individualized discussions with patients, particularly those not on dialysis," he said.
Dr. Jeffrey S. Berns, professor of medicine and pediatrics at the University of Pennsylvania, agreed that use of an ESA must be decided case by case. But to him, the overall condition of a patient is more important in making the decision than whether the patient is on dialysis.
"To go to the extremes, if you have a 95-year-old in a wheelchair, I see no reason to treat," Berns said. "If you have a 32-year-old who is active and wants to remain so, I see no problem in using an ESA to get the hemoglobin up."
One reason why the meta-analysis found so many problems, Berns said, is that studies tend to have few young people in them. "It may be the much older patient populations that were studied," he said. "No matter what you did to them, you may not be able to show much improvement in quality of life."
The U.S. Food and Drug Administration has more on ESAs.
SOURCES: Ajay K. Singh, M.D., associate professor, medicine, Harvard Medical School, and director, renal division and dialysis services, Brigham and Women's Hospital, Boston; Jeffrey S. Berns, M.D., professor, medicine and pediatrics, and assistant chief, renal division, Hospital of the University of Pennsylvania, Philadelphia; May 3, 2010, Annals of Internal Medicine, online
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