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Kidney Week

Abstract: TH-PO976

Efficacy and Safety of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors (HIF-PHIs) in Patients with CKD: Metanalysis of Phase 3 Randomized Controlled Trials

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism

Authors

  • Minutolo, Roberto, Universita degli Studi della Campania Luigi Vanvitelli Scuola di Medicina e Chirurgia, Napoli, Campania, Italy
  • Garofalo, Carlo, Universita degli Studi della Campania Luigi Vanvitelli Scuola di Medicina e Chirurgia, Napoli, Campania, Italy
  • Borrelli, Silvio, Universita degli Studi della Campania Luigi Vanvitelli Scuola di Medicina e Chirurgia, Napoli, Campania, Italy
  • De Nicola, Luca, Universita degli Studi della Campania Luigi Vanvitelli Scuola di Medicina e Chirurgia, Napoli, Campania, Italy
Background

HIF-PHIs are new therapeutic agents for anemia of CKD. We evaluated by metanalysis and meta-regression efficacy and safety of HIF-PHIs in patients with CKD-related anemia.

Methods

We selected phase-3 RCTs comparing HIF-PHIs and ESA in dialysis and non-dialysis CKD patients. Efficacy outcomes were the changes from baseline of hemoglobin (Hb), iron parameters and intravenous iron dose; safety outcomes included cancer, major adverse cardiovascular events (MACE), MACE+ (MACE plus hospitalization for HF, unstable angina or thromboembolism), thrombotic events (deep vein thrombosis, pulmonary embolism), artero-venous fistula (AVF) thrombosis, and death.

Results

In 26 RCTs (N=24,387 patients) included, comparators were long-acting ESA (darbepoetin or CERA) in 17 RCTS and short-acting ESA (epoetin-α or-β) in 9 trials. Summary of difference between HIF-PHI and ESA for efficacy and safety is depicted in Figure 1. Random effect meta-analysis of unstandardized mean difference between HIF-PHIs and ESAs showed a significant change from baseline in Hb levels. Meta-regression analysis showed significantly higher Hb change for HIF-PHIs in younger patients and in studies using short-acting ESA as comparator (+0.21 g/dL, 95%CI, 0.12-0.29 vs -0.01, 95%CI, -0.09-0.07 in studies using long-acting ESA, P<0.001). Heterogeneity was not affected by type of HIF-PHIs. In comparison with ESAs, HIF-PHIs induced a significant decline in hepcidin and ferritin and a significant increase in serum iron and TIBC; IV iron dose was lower with HIF-PHI. Rate ratio of cancer, MACE, MACE+, thrombotic events and death did not differ between HIF-PHIs and ESAs.

Conclusion

In comparison with ESA therapy, HIF-PHIs are effective in correcting anemia and improving with a significant impact on iron metabolism without notable difference among various agents. No safety signals emerge with use of HIF-PHIs.

Summary effects of HIF-PHIs compared with ESA on efficacy and safety measures