Therapy with Erythropoiesis- Stimulating Agents and Renal and Nonrenal Outcomes Anil K. Agarwal, MD a , Ajay K. Singh, MB, FRCP(UK) b, * The use of erythropoiesis-stimulating agents (ESA) in the treatment of the anemia of heart failure or chronic kidney disease (CKD) is currently contro- versial. 1,2 A large number of observational studies have reported an association between the severity of anemia in patients with CKD and heart failure (HF) and outcomes such as mortality and hospital- ization risk. 3–10 These studies are reviewed exten- sively elsewhere. In CKD patients on dialysis and those not on dialysis, higher hemoglobin concen- trations are associated with a lower risk of mortality, cardiovascular complications, and hospitalization. In patients with heart failure, a study by McClellan and colleagues 6 examining a retrospective cohort of 655 Medicare patients admitted to community hospitals for heart failure reported a 2.4% decrease in 1-year risk of death per 1% increase in hematocrit after adjustment for age, sex, race, kidney function, and cardiovas- cular comorbidities (Table 1). Other studies have found an association between anemia and the risk of hospitalization. 7–10 On the other hand, there has been a paucity of evidence from randomized controlled studies to indicate that correction of anemia is associated with benefit. In patients with CKD, several randomized controlled trials (RCTs) indicate that the use of ESA in correcting anemia is associated with increased risk. 11–14 Consequently, we are left with a conundrum: although anemia is common in HF and CKD and observational studies indicate benefit with higher hemoglobin concentrations, treatment with ESA used to target a higher hemoglobin is associated with increased risk of adverse outcomes. For the clinician, the treatment questions are simple: should we be treating CKD and/or HF anemia with an ESA? If so, what level of hemoglobin should be targeted? This article examines the observational data and the recent information from randomized trials that point to increased risk in CKD and HF settings, and whether these disparate results can be explained by exposure to ESAs in this setting. RENAL OUTCOMES IN ANEMIA Anemia is a common complication of CKD and progresses with deterioration of kidney function. 15 Disclosures: Dr Agarwal has received honoraria from Amgen and is an investigator in TREAT. He has received research support from Amgen, Fibrogen, and AMAG. Dr Singh was Principal Investigator of the CHOIR study and a member of the Executive Committee for the TREAT study. He reports receiving consulting income from Amgen, Johnson & Johnson, Fibrogen, and Watson. He reports receiving grant support from Amgen, Johnson & Johnson and Watson. a Division of Nephrology, The Ohio State University, 395 West 12th Avenue, Ground Floor, Columbus, OH 43210, USA b Renal Division, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA * Corresponding author. E-mail address: asingh@rics.bwh.harvard.edu KEYWORDS  Epoetin  Epogen  Erythropoiesis-stimulating agents  CKD  ESRD Heart Failure Clin 6 (2010) 323–332 doi:10.1016/j.hfc.2010.03.006 1551-7136/10/$ – see front matter ª 2010 Elsevier Inc. All rights reserved. heartfailure.theclinics.com