Testing the effects of daprodustat in chronic kidney disease heart failure

Researchers conducted a retrospective study to compare the impact of oral hypoxia-inducible factor prolyl hydroxylase daprodustat (Daprodustat) with conventional injectable erythropoietin (ESA) on heart failure (HF) hospitalization rates in patients with chronic kidney disease (CKD). The study analyzed the ASCEND-D trial (n = 2,964) and the ASCEND-ND trial (n = 3,872), which compared the effects of two treatment options in CKD anemia patients with and without dialysis requirements.

The study identified major risk factors for heart failure hospitalization, including a history of heart failure, diabetes and higher systolic blood pressure. The results showed that the number of first-time hospitalizations for heart failure increased among patients treated with daprostat, regardless of whether they received dialysis, but was not statistically significant. Among patients who did not receive dialysis, the hazard ratio in the daplestat group was HR 1.22 (0.95-1.56, P=0.12), while in patients who received dialysis it was HR 1.10 (0.84-1.45, P=0.47).

In the analysis, the ASCEND-ND trial results showed that in patients with a history of heart failure, the hazard ratio for daporostat was HR 1.37 (0.89-2.11) and in patients without a history of heart failure, HR 1.08 (0.79-1.46) (P-interaction = 0.36). The corresponding results in the ASCEND-D trial were HR 1.52 (0.97-2.38) for those with a history of heart failure and HR 0.93 (0.66-1.30) for those without a history of heart failure (P-interaction = 0.09). A post hoc analysis indicated that among patients not receiving dialysis, the use of daprostat significantly increased overall heart failure hospitalizations, including first and recurrent hospitalizations.

Additionally, dapoxostat did not show a significant effect on the risk of the composite outcome of first heart failure hospitalization or death. Combining all the results, the researchers concluded that daporostat may increase the risk of first heart failure hospitalization in CKD patients compared with conventional ESA, especially in non-dialysis patients and patients with a history of heart failure. Although the difference in this effect did not reach statistical significance, it still requires clinical attention.

Reference materials:https://en.wikipedia.org/wiki/Daprodustat