On September 11, 2007, an FDA panel of health experts declined to recommend the quasi-expected restrictions on the use of the erythropoietin stimulating agents (ESA) in CKD patients.
For years, the three FDA-approved ESAs (Aranesp, Epogen, and Procrit) have been heavily prescribed for anemia without much concern about serious adverse effects. The traditional hemoglobin target ranges have had an upper threshold of 12 g/dL.
Nevertheless, in recent years, there has a been a gradual trend in surpassing this “magic number,” with the thinking (based on observational studies) that this would be in the best interest of the patient (the higher the hemoglobin, the better the survival). ESA overutilization was further encouraged when the NKF revised its Kidney Dialysis Outcomes Quality Initiative (K/DOQI) guidelines on anemia management in early 2006, recommending hemoglobin levels above 11 g/dL, but without any specific upper threshold as long as hemoglobin above 13 g/dL is not targeted proactively.
In November 2006, researchers published the results of two randomized controlled trials in CKD patients not undergoing dialysis (the CHOIR and CREATE studies) suggesting that targeting hemoglobin levels of 13 g/dL or above tended to be associated with more frequent cardiovascular events and deaths.
These results coincided with a cross-sectional analysis showing that for-profit dialysis companies prescribed more ESA than their non-profit counterparts. Additional reports disclosed that 20% to 25% of the profit margin of the for-profit dialysis organizations came from the ESA trade and utilization.
The rush to demonize ESA and the companies that profit from ESA might have clouded our fair judgment of the risks and benefits associated with anemia treatment. While most clinical trials, and a recent observational study by Regidor and colleagues, have found that hemoglobin above 13 g/dL is associated with worsening survival, there is no convincing data that hemoglobin in moderate ranges such as 11.5 to 12.9 g/dL is deleterious.
Younger or less comorbid dialysis patients may benefit more from such moderate hemoglobin ranges than from levels below 12 g/dL. Calling any hemoglobin value above 12 as “badly high” may not be consistent with the “do-no-harm” principle in medicine. When it comes to anemia management of CKD patients, the highest priority is patient benefit and patient survival. The FDA panel decision may be based on such considerations.