Daprodustat vs Recombinant Human Erythropoietin for Anemia and Cardiovascular Safety in Dialysis-Dependent and Non-Dialysis-Dependent CKD Patients - A Systematic Review and Meta-analysis

Background: Anemia is a prevalent complication in chronic kidney disease (CKD) that remains challenging to manage effectively. Daprodustat was recently approved for anemia in CKD. This meta-analysis aims to provide evidence-based insights for the clinical use of daprodustat in CKD-related anemia. Method: A systematic review and meta-analysis were conducted in accordance with the PRISMA 2020 guidelines, with searches conducted in databases such as PubMed and ClinicalTrials.gov, encompassing studies published up to August 30, 2024. Data from 12 randomized controlled trials involving 9,278 CKD patients (both dialysis-dependent (DD) and non-dialysis-dependent (NDD)) were analyzed. Results: Daprodustat significantly increased hemoglobin (Hb) levels compared to placebo in both NDD (MD = 1.92, 95% CI [0.67, 3.02], p = 0.001) and DD (MD = 1.72, 95% CI [0.34, 3.65], p = 0.01) patients. However, no significant difference in Hb levels was observed between daprodustat and recombinant human erythropoietin (rhEPO) (MD = 0.05, 95% CI [−0.10, 0.21], p = 0.50). Daprodustat improved iron metabolism by significantly lowering hepcidin and increasing total ironbinding capacity (TIBC) compared to rhEPO. Cardiovascular safety analysis showed no significant difference in major adverse cardiovascular events (MACE) between daprodustat and rhEPO (RR = 1.02, 95% CI [0.92, 1.14], p = 0.83), though a significant reduction in MACE incidence was observed in DD patients (RR = 0.98, 95% CI [0.87, 1.15], p = 0.02). Serious adverse events were significantly lower with daprodustat compared to rhEPO (RR = 0.82, 95% CI [0.66, 0.84], p = 0.02 in DD; RR = 0.61, 95% CI [0.48, 0.78], p = 0.008 in NDD patients). Conclusion: Daprodustat offers a promising alternative to traditional anemia treatments in CKD, with efficacy comparable to rhEPO and a favorable cardiovascular safety profile, which marks its potential as a valuable therapeutic option.