Daprodustat for the Treatment of Anemia in Patients Undergoing Dialysis
In the ASCEND-D phase 3 trial, the oral HIF prolyl hydroxylase inhibitor daprodustat was noninferior to erythropoiesis-stimulating agents for both hemoglobin correction and major adverse cardiovascular events in patients with anemia of chronic kidney disease undergoing dialysis.
Background
Anemia is common in chronic kidney disease, and recombinant erythropoietin and its derivatives have been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors are oral agents that stimulate endogenous erythropoietin production and offer a potential alternative to injectable erythropoiesis-stimulating agents (ESAs).
Study design
This randomized, open-label, phase 3 trial assigned 2964 patients with CKD undergoing dialysis and a hemoglobin level of 8.0 to 11.5 g per deciliter to receive oral daprodustat or an injectable ESA (epoetin alfa for hemodialysis or darbepoetin alfa for peritoneal dialysis). The two primary outcomes were the mean change in hemoglobin from baseline to weeks 28 through 52 and the first occurrence of a major adverse cardiovascular event (MACE), a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke.
Key findings
The mean change in hemoglobin was 0.28 g per deciliter in the daprodustat group versus 0.10 g per deciliter in the ESA group (difference 0.18; 95% CI 0.12 to 0.24), meeting the noninferiority margin. Over a median follow-up of 2.5 years, a MACE occurred in 25.2% of the daprodustat group and 26.7% of the ESA group (hazard ratio 0.93; 95% CI 0.81 to 1.07), also meeting the prespecified noninferiority margin, with similar rates of other adverse events between groups.
Clinical implications
Among dialysis patients with anemia of CKD, daprodustat was noninferior to ESAs for both hemoglobin response and cardiovascular safety, supporting its use as an oral alternative to injectable agents. Daprodustat received FDA approval in 2023 for patients on maintenance dialysis; subsequent analyses noted a numerically greater number of heart failure hospitalizations with daprodustat, so long-term safety surveillance remains relevant.
Category
Research
Source
N Engl J Med
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