Safety and Efficacy of Vadadustat Versus Darbepoetin Alfa for Chronic Kidney Disease-Related Anemia in Patients Receiving Dialysis by Baseline Erythropoiesis-Stimulating Agent Dose
Abstract
Introduction: Erythropoiesis-stimulating agents (ESAs) and iron supplementation are standard treatments for chronic kidney disease (CKD)-related anemia. Targeting higher hemoglobin values in CKD increases cardiovascular risk. Whether the increased risk is from higher ESA doses or higher hemoglobin levels is uncertain, but alternative therapies are sought for patients requiring high ESA doses. Phase 3 INNO2VATE trials in patients with dialysis-dependent CKD (DD-CKD) demonstrated vadadustat's noninferiority compared with darbepoetin alfa. To determine vadadustat's potential to treat anemia, including in patients requiring high ESA doses, its safety and efficacy were compared with those of darbepoetin alfa across prespecified baseline ESA dose subgroups in the prevalent DD-CKD INNO2VATE trial.
Methods: We compared the safety and efficacy of vadadustat versus darbepoetin alfa across prespecified baseline ESA dose subgroups (low [≤ 90 U/kg/week], intermediate [> 90 and 2VATE prevalent trial. The primary safety endpoint was time to first adjudicated major adverse cardiovascular event (MACE). Primary and secondary efficacy endpoints were mean hemoglobin level change from baseline at weeks 24-36 and weeks 40-52, respectively.
Findings: Compared with darbepoetin alfa, first MACE hazard ratios for vadadustat were 0.99 (95% CI, 0.81-1.23), 0.93 (95% CI, 0.74-1.18), and 0.62 (95% CI, 0.34-1.14) for low, intermediate, and high baseline ESA dose subgroups, respectively (interaction p =…
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