Epoetin therapy can be administered intravenously (IV) or subcutaneously (SC). The route of epoetin administration has important implications in terms of the dose, frequency of administration, costs, and, potentially, outcomes. In a recent meta-analysis, the investigators found that the SC route offers a substantial reduction in dose without a reduction in safety or effectiveness. In a 1993 controlled European multicenter study, administration of SC epoetin did not result in increased hypertension or cardiovascular disease as a cause of death among the study population. According to the authors, the different pharmacokinetics, and lower dose of SC epoetin might be responsible for an 'even better safety profile' compared with IV administration (see Klinkman H, Wieczorek L, Scigalla P. Adverse events of subcutaneous recombinant human erythropoeitin therapy: Results of a controlled multicenter European study. Artif Organs 1993;17:219-225).
All current guidelines, including the U.S.-generated K/DOQI and the European and Canadian national guidelines for anemia management, recommend SC administration based on best evidence. However, 90% of all patients in the U.S. still receive epoetin intravenously. Although it has been clearly established that SC administration of epoetin requires a 25-50% smaller dose to achieve the same hematocrit outcome, the potential impact of SC administration on other patient clinical outcomes has not been previously investigated.
The goal of MTPPI's research in this area is to examine cardiovascular-related and other clinical patient outcomes related to route of administration of epoetin therapy among maintenance hemodialysis patients. The choice of epoetin route of administration is a complex issue involving consideration of patient clinical and facility characteristics. Specifically, our research has three primary objectives:
1) To determine the role of route of administration on anemia management;
2) To examine the (cross-sectional) association between blood pressure and route of administration, assuming hypertension is one possible intermediate pathway resulting in cardiovascular disease; and
3) To identify the influence of route of administration on patient outcomes, specifically, cardiovascular-related complications (evidenced by hospitalizations and outpatient encounters for cardiovascular disease) and mortality (using cardiovascular disease as well as all-cause mortality).