Hemodialysis (HD) patients who receive erythropoietin subcutaneously rather than intravenously are at lower risk of death, hospitalization for cardiovascular complications, or both, according to a new study.

The study, led by Daniel G. Wright, MD, of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda,Md., included 62,710 adult HD patients treated with either intravenous (IV) or subcutaneous (SC) epoetin alfa and followed up for 24 months. Subjects were enrolled in the Centers for Medicare and Medicare Services (CMS) ESRD Clinical Performance Measures (CPM) Project from 1997 to 2005.

Patients managed with IV epoetin had an 11% increased risk of a composite outcome of death or hospitalization for acute myocardial infarction, congestive heart failure, and stroke within 1 year compared with those managed with SC epoetin after adjusting for potential confounders, the investigators reported online ahead of print in the Clinical Journal of the American Society of Nephrology.

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As expected, epoetin doses used to achieve equivalent hemoglobin responses, on average, were 25% higher with IV versus SC administration, the authors stated.

The authors concluded that their study provides evidence that routine use of SC rather than IV epoetin to treat anemia in HD patients “could enhance survival and reduce hospitalizations for cardiovascular complications by minimizing epoetin dosing.”

Assuming that their study findings accurately represent all ESRD patients in the United States from 1997 to 2005, they estimated that nearly 30,000 early deaths and/or hospitalizations for cardiovascular complications might have been avoided had all patients been managed with SC epoetin.

Dr. Wright and his colleagues noted that concerns about the development of drug-associated pure red cell aplasia (PRCA) have led to recommendations that HD patients be treated with IV rather than SC epoetin. Therefore, they examined records from the CMS for occurrences of PRCA among the study subjects within 5 years after their entry into the ESRD CPM Project. Prior to 2008, no specific ICD-9 code was defined for PRCA, but this diagnosis was included among other forms of acquired aplastic anemia (248.8), the authors pointed out. They screened records for this ICD-9 code and then used other diagnosis, procedure, and treatment codes to look for possible cases of PRCA using criteria described by Alan J. Collins, MD, and colleagues in the American Journal of Kidney Diseases (2004;43:464-470). These criteria included records of bone marrow examination, persistent anemia, and repeated red cell transfusions but not other causes of marrow failure.

Of 57,602 patients treated with IV epoetin, 92 (0.16%) had a 284.8 code recorded at some time within 5 years of entry to the CPM Project compared with 3 (0.06%) of 5,108 patients managed with SC epoetin. Of the entire cohort, however, only 1 case of possible PRCA fulfilled the criteria of Collins et al during 201,655 patient-years of follow-up.