Treatment of anemia with darbepoetin prior to dialysis initiation and clinical outcomes: Analyses from the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT)

Rationale & Objective: Evidence from clinical trials to guide patient preparation for maintenance dialysis therapy is limited. Although anemia is associated with mortality and cardiovascular (CV) disease in individuals initiating maintenance dialysis therapy, it is not known if treatment of anemia before dialysis therapy initiation with erythropoiesis-stimulating agentsalters outcomes. Study Design: Post hoc analysis of a randomized controlled trial. Setting & Participants: Participants with type 2 diabetes and chronic kidney disease who progressed to dialysis therapy (n = 590) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Exposure: Randomized treatment assignment (darbepoetin vs placebo). Outcomes: All-cause mortality, CV mortality, nonfatal myocardial infarction, heart failure, and stroke within the first 180 days of dialysis therapy initiation. Analytical Approach: Proportional hazards regression. Results: Overall, 590 of 4,038 (14.6%) participants initiated dialysis therapy during the trial (n = 298 and 292 in the darbepoetin and placebo groups, respectively). Corresponding hemoglobin levels were 11.3 ± 1.6 and 9.5 ± 1.5 g/dL (P < 0.001). Death from any cause occurred in 31 (10.4%) participants assigned to darbepoetin and 28 (9.6%) assigned to placebo (HR, 1.16; 95% CI, 0.69-1.93), while death from CV causes occurred in 15 (5.0%) and 13 (4.5%) participants, respectively (HR, 1.21; 95% CI, 0.58-1.93). There were no differences in risk for nonfatal myocardial infarction or heart failure. Stroke occurred in 8 (2.8%) participants assigned to darbepoetin and 1 (0.3%) assigned to placebo (HR, 8.6; 95% CI, 1.1-68.7). Limitations: Post hoc analyses of a subgroup of study participants. Conclusions: Despite initiating dialysis therapy with a higher hemoglobin level, prior treatment with darbepoetin was not associated with a reduction in mortality, myocardial infarction, or heart failure in the first 180 days, but a higher frequency of stroke was observed. In the absence of more definitive data, this may inform decisions regarding the use of erythropoiesis-stimulating agents to treat mild to moderate anemia in patients with type 2 diabetes and chronic kidney disease nearing dialysis therapy initiation.