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Anemia of chronic kidney disease: CHOIR and the FDA

Nature Clinical Practice Nephrology volume 3, pages 406–407 (2007)Cite this article

The publication of the results of the CHOIR study1 has been followed by several reports about the risks associated with erythropoiesis-stimulating agents (ESAs) in patients with cancer, patients undergoing routine spinal surgery, and critically ill patients. These reports have prompted growing disquiet among health care professionals about the safety of ESAs, and have culminated in the US FDA issuing a Public Health Advisory.2 The FDA has also demanded that its strongest safety warning—a 'black box' or 'boxed' warning—be included on the labeling of these drugs. The most controversial of the FDA's recommendations is that the lowest dose of ESA needed to prevent blood transfusion should be used. Furthermore, the FDA instructs doctors to “understand that ESAs should not be given to treat the symptoms of anemia”. Given that most clinicians prescribe transfusions for the symptoms of anemia, how should this advice be interpreted?

The FDA has cited data from the CHOIR study, several oncology studies and a study of patients who were undergoing routine spinal surgery to justify the black box warning.2 The CHOIR study enrolled 1,432 patients and reported a 34% higher risk of death or cardiovascular events with a high hemoglobin target level (135 g/l [13.5 g/dl]) than with a lower hemoglobin target level (113 g/l [11.3 g/dl]; P = 0.03). The CHOIR study also showed no benefit in quality of life with the higher hemoglobin target. These results are concordant with those of the Normal Hematocrit study,3 published nearly a decade earlier. In addition, results of the CREATE study,4 published in the same issue of the New England Journal of Medicine as the CHOIR results, showed a trend towards greater cardiovascular risk with a high hemoglobin target than with a lower target. A recent meta-analysis reported that a hemoglobin target of >120 g/l (>12.0 g/dl) was associated with a 17% increase in mortality risk in patients with chronic kidney disease (CKD; both predialysis patients and those on dialysis).5 Despite the totality of evidence, some clinicians remain doubtful as to whether targeting higher hemoglobin concentrations in CKD patients really is harmful. As Strippoli and co-workers6 have said: “Surprisingly, faced with the coherence of all the available evidence, many try to downplay these key findings and their response indicates strongly held beliefs discordant with what is now a sizeable and consistent body of evidence that higher haemoglobin targets are not better than lower.”

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  1. Renal Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA asingh@partners.org

Authors and Affiliations

  1. AK Singh is Clinical Chief of the Renal Division, Director of Dialysis Services and a Physician at the Brigham and Women's Hospital, and an Associate Professor of Medicine at Harvard Medical School, Boston, MA, USA.,

    Ajay K Singh

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Competing interests

Dr Singh reports having received consulting fees from Abbott, Amgen, Horizon Blue Cross Blue Shield, Merck (Germany), Ortho Biotech Clinical Affairs, Roche and Watson, and lecture fees from Abbott, Amgen, Genzyme, Ortho Biotech Clinical Affairs, Pfizer, Roche, Scios and Watson; having served on advisory boards for Advanced Magnetics, Amgen, Ortho Biotech Clinical Affairs, Roche and Watson; and having received grant support from Amgen, Baxter, Dialysis Clinic, Genentech, the National Institutes of Health, Ortho Biotech Clinical Affairs, Roche and Watson.

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Singh, A. Anemia of chronic kidney disease: CHOIR and the FDA. Nat Rev Nephrol 3, 406–407 (2007). https://doi.org/10.1038/ncpneph0539

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