Daprodustat for patients with heart failure and renal anemia: A pilot multicenter, open-label, randomized controlled study.

Abstract

Background: Anemia and renal failure, common comorbidities in patients with heart failure (HF), are associated with increased mortality. Hypoxia-inducible factor prolyl hydroxylase inhibitors, such as daprodustat, treat renal anemia by stimulating erythropoiesis and enhancing iron availability. However, its efficacy in treating HF with renal anemia remains to be determined.

Methods: This pilot, multicenter, open-label, randomized controlled trial was conducted in five hospitals in Japan. Patients with HF, anemia (hemoglobin, 7.5-11 g/dL), and renal impairment (estimated glomerular filtration rate, <60 mL/min/1.73 m²) not requiring hemodialysis were randomized 1:1 to receive daprodustat or standard of care. The primary endpoint was the hemoglobin level at 16 weeks. The secondary endpoints included blood transfusion rates, alleviation of HF symptoms, changes in N-terminal pro-B-type natriuretic peptide and iron-related biomarkers, and cardiac structural and functional changes.

Results: Twenty-one patients were randomized between March 2022 and November 2023. At 16 weeks, the mean hemoglobin level was significantly higher in the daprodustat group (12.1 ± 0.73 g/dL) than in the standard of care group (10.3 ± 0.97 g/dL, p < 0.001). Serum iron, ferritin, hepcidin, and transferrin saturation levels were significantly lower, whereas N-terminal pro-B-type natriuretic peptide levels were significantly higher in the daprodustat treatment group. Kansas City Cardiomyopathy Questionnaire Total Symptom Score improvement (44.4 % vs. 55.6 %, p = 0.99) and structural and functional cardiac parameters showed no significant differences.

Conclusions: Daprodustat effectively increases hemoglobin levels and modifies iron metabolism by decreasing hepcidin levels and increasing iron utilization in patients with HF and renal anemia.