Are there advantages of daprodustat over erythropoiesis-stimulating agents (ESAs) in treating anemia associated with chronic kidney disease (CKD)?

Anemia is common in CKD and increases the risk of developing heart disease. Although ESAs relieve the symptoms of anemia, they have adverse effects and do not reduce the adverse outcomes associated with anemia. This evaluation is of the phase 3 ASCEND clinical trials of the hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor daprodustat versus ESAs in subjects with CKD undergoing dialysis or not. Daprodustat was non-inferior to ESAs in increasing hemoglobin, and in the incidence of cardiovascular events and adverse effects. Daprodustat is effective in subjects who are hyporesponsive to ESAs, and this is one circumstance when daprodustat may be preferred to ESAs. However, to become a widely used medicine in subjects with CKD responsive to ESAs, daprodustat needs to be well tolerated, used by a high percentage of subjects over a long time, and be superior to ESAs in improving clinical outcomes. As this may not be the case, there is not a strong basis for recommending daprodustat over ESAs. The other 'dustats' (roxadustat, vadadustat) have also not been shown to be superior to the ESAs, and none have been approved by the FDA to date.