Effects of large ESA and iron doses vary with hematocrit level

More aggressive treatment with erythropoiesis-stimulating agents (ESAs) and iron benefitted dialysis patients with lower hematocrit levels but increased mortality risks in the patients with high hematocrit, a new study found.

Researchers used data from the Medicare end-stage renal disease program to analyze the anemia management practices of U.S. dialysis centers. The main outcome was all-cause mortality, and the study found the highest mortality rates in patients with hematocrit below 30% (2.1% monthly) and the lowest (0.7%) in those with hematocrit of 36% or above. The study was published in the March 3 Journal of the American Medical Association.

Among the patients in the under 30% hematocrit group, the lowest mortality rates were seen in dialysis centers that used larger doses of ESAs. Similarly, more use of iron was associated with lower mortality in patients with hematocrit below 33%. However, for patients with hematocrit of 36% or higher, the centers that used ESAs and iron more intensively had higher mortality rates. For ESAs, the association between bigger doses and higher mortality extended to patients with hematocrit between 33% and 35.9%.

The cause of these findings is uncertain, the study authors said. It's unlikely that greater mortality relates directly to higher doses of ESA and iron, since the largest doses were given to the patients with the lowest hematocrit levels. Previous trials have found higher mortality risk associated with targeting of higher hematocrit levels, the authors noted. They concluded that, whatever the cause, greater use of ESAs and iron in patients with higher hematocrit levels is problematic and further research should be conducted to identify optimal treatment algorithms.

The FDA recently required the development of a risk management program for ESAs, as reported in a recent issue of ACP InternistWeekly.