Erythropoiesis-stimulating agents and heart failure.

Anemia is a common comorbidity in heart failure (HF) patients. Its occurrence and severity are associated with worse prognosis. Although the etiology of anemia is multifactorial, inappropriate erythropoietin (EPO) production and/or bone-marrow resistance to EPO appear crucial in majority of anemic HF patients. Consequently, treatment based on this pathophysiological background may prove to be most effective and beneficial. In a number of smaller clinical studies, administration of erythropoiesis-stimulating agents (ESAs) to anemic HF patients improved a number of surrogate endpoints, including left ventricular function, exercise capacity, renal function, and different quality of life parameters. However, two larger, phase II studies, did not fully confirm these promising results. Furthermore, many concerns have been raised on the safety of ESAs after the recent publication of studies correcting anemia in patients with chronic kidney disease (CKD). On the other hand, chronic HF population varies significantly from CKD patients, with different comorbidities, renal function, and etiology of anemia. Moreover, ESAs have been shown to possess robust nonhematopoietic effects in the heart, namely inhibition of apoptosis and stimulation of neovascularization. Therefore, large-scale trials with ESAs are required to examine the effect and safety of anemia treatment in HF patients.