Cardiovascular events by different target hemoglobin levels in ESA-hyporesponsive hemodialysis patients: a multicenter, open-label, randomized controlled study

Background The incidence of cardiovascular (CV) events is high in hemodialysis (HD) patients and is associated with hyporesponsiveness to erythropoiesis-stimulating agents (ESAs). However, there are no recommended target hemoglobin ranges for ESA-hyporesponsive patients. Methods We randomly assigned 304 ESA-treated HD patients with ESA hyporesponsiveness to a proactive treatment group (target hemoglobin level 11 g/dL) or maintenance treatment group (target hemoglobin level 9–10 g/dL), both of which received epoetin beta pegol. The primary outcome was time to the first CV event. CV events included cardiac death, heart failure, and acute coronary syndrome requiring hospitalization. The patients were followed for 24 months. Results The proactive and maintenance treatment groups had mean baseline hemoglobin levels of 9.34 and 9.32 g/dL, respectively. Mean hemoglobin levels during the observation period were 10.58 and 10.26 g/dL ( P < 0.001), and mean durations of hemoglobin level > 10.5 g/dL were 11.5 and 8.6 months ( P < 0.001), respectively. Cox proportional hazards analysis demonstrated a significantly lower risk of CV events in the proactive group (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.19–0.96). This lower risk was driven by lower incidence of hospitalization-required congestive heart failure. A longer duration of hemoglobin level > 10.5 g/dL was associated with a lower risk of CV events (HR, 0.92/month; 95% CI, 0.87–0.98). Conclusions Targeting hemoglobin levels of 11 g/dL with epoetin beta pegol reduces CV risk in Japanese HD patients with ESA hyporesponsiveness. Trial registration : University Hospital Medical Information Network (UMIN) database (UMIN000010138), registered on March 1, 2013.