MP597HIGH VERSUS LOW DOSE ERYTHROPOIESIS-STIMULATING AGENTS IN PEOPLE WITH END-STAGE KIDNEY DISEASE TREATED WITH HAEMODIALYSIS (C.E. DOSE): AN OPEN-LABEL, PRAGMATIC,MULTICENTRE, PARALLEL-GROUP RANDOMISED CONTROLLED TRIAL

Abstract

Introduction and Aims: The adverse effects of a high hemoglobin target achieved through erythropoiesis-stimulating agent (ESA) in CKD have been established, but it is uncertain whether these effects are mitigated and the quality of life benefits maintained when a fixed dose strategy is used. Methods: .E. DOSE was a multicenter, pragmatic, non-blinded, randomised controlled, parallel-group trial that randomised 656 hemodialysis patients with anemia to receive either high dose (18,000 IU epoetin alfa or epoetin beta or 90 mcg darbepoetin alfa per week) or low dose (4000 IU epoetin alfa or epoetin beta or 20 mcg darbepoetin alfa per week) ESA. Rescue dose adjustments were made when the hemoglobin level moved outside the safety range of 9 5-12 5 g/dl. The primary outcome was the composite of death or a CV event (non-fatal myocardial infarction, non-fatal stroke, or hospitalization for acute coronary syndrome, transient ischemic attack, unplanned percutaneous coronary intervention or peripheral revascularization). Secondary endpoints included individual CV events, health-related quality of life (HRQOL), blood transfusions, blood pressure, and hemoglobin levels (ClinicalTrials.gov, number NCT00827021). Results: The study was completed early at 12 months of a planned 48 due to slow recruitment and convergence of ESA dose in the two groups. During follow up there were 55 deaths or major CV events in the high dose group (16.6%) and 46 deaths or major CV events in the low dose group (14.2%; hazard ratio 1.19, 95% CI 0.81-1.77). The number of deaths did not differ between groups (40 deaths versus 35 deaths; HR 1.21; 95% CI 0.77-1.91). Patients assigned to high dose therapy had a lower risk of blood transfusion (HR 0.51; 0.28-0.93). There was no difference in HRQOL (mean difference in physical composite score at 12 months 1 70, 95% CI -0 95 to 4 35) or blood pressure between high and low dose therapy. Conclusions: Fixed high dose ESA therapy has uncertain effects on mortality and cardiovascular events without improving health-related quality of life. Commencing low dose ESA therapy may be preferred in the presence of uncertain treatment harms with high dose therapy and lack of benefit on quality of life, although a low dose strategy will incur higher risks of blood transfusion.