Trick or TREAT? More Condemning Evidence Against ESAs

Abstract

The recent publication of the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) serves confounding and perhaps condemning evidence against the use of erythroid stimulating agents (ESAs) in predialysis patients with chronic kidney disease. However, the additional value of the TREAT results is questionable, given the design of the trial and the background evidence surrounding the use of ESAs that has amassed since 2006. This objective of this commentary is to summarize and interpret the TREAT trial in light of current practice and recent literature and to provide a suggested approach to the use of ESAs in the long-term care population going forward. TREAT was conducted between 2004 and 2009 in 4038 diabetic patients with chronic kidney disease and anemia; 2012 patients were randomized to darbepoetin alfa at a dose targeted to achieve a serum hemoglobin value of 13 g/dL, and 2026 were randomized to placebo with a darbepoetin rescue option when hemoglobin was less than 9 g/dL. The primary endpoint was a composite outcome of death, cardiovascular events (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia), or end-stage renal disease. At baseline, the placebo and treatment groups were well matched for underlying conditions, laboratory values, and concurrent medications. Patients were monitored for 2 years. There was no difference in composite endpoints achieved between the treated and untreated arms, with the exception that those treated to a target hemoglobin of 13 g/dL experienced nearly a twofold increase in fatal or nonfatal stroke (hazard ratio 1.92 [95% CI 1.38–2.68], P .001). Darbepoetin administration was associated with a reduction in red-cell transfusions and a modest improvement in patient-reported fatigue compared with the placebo group. TREAT was designed and enrollment began before the results of the Cardiovascular Risk