Anemia is a common comorbidity in patients with
heart failure and is associated with worse long-term outcomes. Although the cause of
anemia in
heart failure is unclear, the weight of evidence suggests that renal dysfunction, along with neurohormonal and proinflammatory
cytokine activation in
heart failure, favors the development of
anemia of
chronic disease, with defective
iron utilization, inappropriate
erythropoietin production, and depressed bone marrow function. Similarly, the mechanisms by which
anemia worsens
heart failure outcomes are unknown but may be related to increased myocardial workload. If
anemia is a mediator and not just a marker of poor outcomes, correcting
anemia could become an important and novel therapeutic target to improve long-term outcomes in such patients. Indeed, several small-sized studies have shown the beneficial effects of empirically treating
anemia in
heart failure patients with recombinant
erythropoietin and intravenous
iron. However, the ideal threshold at which
therapy should be initiated and the extent of correction considered safe and desirable in the individual patient with
heart failure need to be known. These issues become more important because of increasing safety concerns that recombinant
erythropoietin therapy for treating
anemia may be associated with adverse cardiovascular outcomes in patients with
chronic kidney disease and may worsen
cancer in patients receiving
chemotherapy to treat various types of
cancer. Therefore, further prospectively designed studies are required to address some of these questions. Fortunately, 2 large mortality morbidity trials, TREAT (Trial to Reduce Cardiovascular Events with
Aranesp Therapy) in patients with
chronic kidney disease and RED-HF (Reduction of Events with
Darbepoetin alfa in
Heart Failure) in
heart failure patients, are in progress and are likely to provide definitive answers.