SAN DIEGO—Studies of anemia management in CKD patients have shown an increased risk of death and cardiovascular morbidity associated with high hemoglobin (Hb) targets, but new data presented here during Renal Week suggest that the presence of comorbidities such as heart failure or diabetes renders these risks clinically undetectable.
“Clinically, these results support an even greater individualization of care than seen in the past as well as potentially placing a greater emphasis on functional outcomes in these subgroups,” said lead investigator Lynda A. Szczech, MD, Associate Professor of Nephrology at Duke University Medical Center in Durham, N.C.
She and her colleagues conducted a subgroup analysis of patients in the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) study, a randomized trial comparing the effect of treatment with epoetin alfa to two Hb targets (11.3 and 13.5 g/L) on the composite end point of death, heart failure hospitalization, stroke, and myocardial infarction in 1,432 patients with CKD and anemia.
After adjusting for potential confounders, Dr. Szczech’s team observed no increased risk in the composite end point of cardiovascular outcomes associated with higher as compared to lower target Hb levels among participants with heart failure. Patients without heart failure, however, had an 86% increased risk.
Similarly, patients with diabetes mellitus did not have an increased risk associated with higher Hb targets. While patients without diabetes mellitus did have an increased risk associated with the higher goal, the interaction between diabetes and treatment arm, did not reach conventional levels of statistical significant in multivariable analyses.
Dr. Szczech and her group also examined the interaction between diabetes and heart failure and hemoglobin goal. Patients without a history of either prior heart failure or diabetes had a twofold increased risk associated with the higher hemoglobin goal. Patients with diabetes but no history of heart failure had a 75% increased risk associated with the higher goal, and subjects with prior heart failure with or without diabetes were not at increased risk.
“It is unclear whether the mechanism for this differential treatment effect might be due to the stronger effect of the comorbidity on outcome,” Dr. Szczech said. “The clinical trials in anemia management may appear superficially dissimilar but in fact are all part of a very complex puzzle that is starting to take shape.”
These results indicate that patients with diabetes and heart failure are different from “all-comers.” Therefore, CHOIR and the Trial to Reduce Cardiovascular Endpoints with Aranesp Therapy (TREAT) complement each other and do not have different conclusions, Dr. Szczech said.
In TREAT, which is a phase 3 study, researchers looked at cardiovascular and renal outcomes of darbepoetin (Aranesp) in CKD patients with type 2 diabetes and anemia. Investigators randomized 4,038 such patients to receive darbopoetin or placebo. The treatment target was an Hb level of 13 g/dL. Preliminary results did not show a significant adverse effect on the primary end points of all-cause mortality or cardiovascular morbidity compared with placebo.