Erythropoietins: aim for lower haemoglobin levels

Dosage instructions for the use of erythropoiesis-stimulating agents (erythropoietins) in patients with chronic kidney disease have been updated in line with evidence that higher haemoglobin levels may be associated with an increased risk of morbidity and mortality.

The three erythropoietins currently available in Australia are erythropoietin alfa (Eprex), erythropoietin beta (NeoRecormon), and darbepoetin alfa (Aranesp). They are approved for the treatment of anaemia associated with chronic renal failure and with the treatment of certain malignancies.

Recent studies and a meta-analysis have compared outcomes in patients with chronic kidney disease treated with an erythropoietin and randomised to achieve either a normal or subnormal haemoglobin level.^1,2,3

The larger of the two randomised studies showed a lower incidence of adverse cardiovascular outcomes (death, myocardial infarction, hospitalised heart failure, or stroke) in the subnormal (113 g/L) compared to the normal (135 g/L) target haemoglobin group.¹

The second study showed no difference in cardiovascular outcomes between the two groups,² and the meta-analysis of nine randomised trials showed a lower all-cause mortality and lower incidence of arteriovenous access thrombosis in patients in the lower target haemoglobin groups.³

Product information documents for the three erythropoietins have been amended to indicate a target haemoglobin not exceeding 120 g/L in patients with anaemia due to chronic kidney failure.

The dose of erythropoietin should be adjusted to maintain the lowest haemoglobin level needed to avoid the need for blood transfusions.

Reference

1. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan. Correction of anemia with epoetin alfa in chronic kidney disease. NEJM 2006; 355: 2085-2098
2. Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, Burger HU, Scherhag A. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. NEJM 2006; 355: 2071-2084.
3. Phrommintikul A, Haas SJ, Elsik M, Krum H. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet 2007; 369: 381-388.

Reference
The Australian Adverse Drug Reactions Bulletin, Volume 26, Number 6 (December 2007)