The Controversy Over Anemia Drugs (ESAs)
Two of the world’s largest drug companies are paying hundreds of millions of dollars to doctors every year in return for giving their patients anemia medicines, which regulators now say may be unsafe at commonly used doses.To summarize: the article not only implies that medications like Epogen, Procrit, and Aranesp -- used to increase the blood count to treat anemia -- are given needlessly, but that doctors and others have strong financial incentives to prescribe these medications and have disregarded the safety of patients.
One physician I know, a nephrologist, was furious at this article. Prior to the advent of Epogen (erythropoetin) and other erythropoiesis-stimulating agents (ESAs), he said, patients with kidney disease on dialysis were routinely dependent on blood transfusions. (Anemia is a common side effect of kidney disease.) They routinely felt awful. In fact, it wasn't until the widespread correction of anemia with Epogen that physicians realized that it wasn't the kidney disease itself that was making dialysis patients feel awful -- it was often the accompanying anemia. The article in the New York Times, he complained, failed to stress this important benefit of Epogen and other drugs.
Previous studies looking at qualify of life of kidney disease patients have suggested that the optimal hemoglobin is 11 - 12 g/dL, and for many years, this range has been the target for therapy. Some physicians assumed that higher hemoglobin levels were likely to be better for certain patients. But recently, studies in kidney disease and cancer patients have noted an increase in heart attacks, blood clots, and other complications when ESAs are given to maintain a hemoglobin of above 12 - 13 g/dL.
From the FDA web site:
In light of new information from recent studies, the FDA and major medical societies are reviewing their guidelines and are expected to issue revised guidelines on the use of medications to treat anemia in the next few months.
Patients currently using or considering the use of an ESA should know the following:
- A higher chance of death and an increased rate of tumor growth were reported in patients with advanced head and neck cancer receiving radiation therapy and in patients with metastatic breast cancer receiving chemotherapy, when ESAs were given to maintain hemoglobin levels of more than 12 g/dL.
- A higher chance of death was reported and no fewer blood transfusions were received when ESAs were given to patients with cancer and anemia not receiving chemotherapy.
- A higher chance of death was reported and an increased number of blood clots, strokes, heart failure, and heart attacks was reported in patients with chronic kidney failure when ESAs were given to maintain hemoglobin levels of more than 12 g/dL.
- A higher chance of blood clots was reported in patients who were scheduled for major surgery and given ESAs.
- ESAs are not approved for treatment of the symptoms of anemia, such as fatigue in patients with cancer, surgical patients and patients with HIV.
- If you have any questions you should talk with your health care provider.
Important study results include the following:
- Patients with chronic kidney failure had an increased number of deaths and of non-fatal heart attacks, strokes, heart failure, and blood clots when ESAs were adjusted to maintain higher red blood cell levels (hemoglobin more than 12 g/dL).
- Patients with head and neck cancer receiving radiation therapy had faster tumor growth when ESAs were adjusted to maintain hemoglobin levels higher than 12 g/dL.
- Patients with cancer not receiving chemotherapy died sooner and had no fewer blood transfusions when ESAs were given according to the dosing recommendations for cancer patients receiving chemotherapy.
- Patients scheduled for orthopedic surgery who received ESAs to reduce blood transfusions during and after surgery had more blood clots than those not given an ESA.
Physicians who prescribe ESAs should consider the important study results above and:
- Understand that ESAs are given to decrease the need for red blood cell transfusions;
- Consider both the risks of transfusions and those of ESAs when deciding to prescribe an ESA;
- Adjust the dose of ESA to maintain the lowest hemoglobin level necessary to avoid the need for transfusions.
- Monitor patients’ hemoglobin levels to ensure they do not exceed 12 g/dL;
- Understand that ESAs have not been shown to improve the outcomes of chemotherapy treatment (e.g., better tumor shrinkage, delay in tumor growth or longer time for survival); and
- Understand that in patients with cancer whose anemia is caused by chemotherapy and in patients with HIV whose anemia is caused by AZT (zidovudine), there are no data to support claims of improvement in health-related quality of life, including effects on fatigue, energy or strength.