Angiotensin Converting Enzyme Inhibitors (ACE-I) and Angiotensin Receptor Blockers (ARB) have long been considered standard therapy in the medical management of congestive heart failure and diabetes due to their beneficial effects in preventing progression of cardiac remodeling and diabetic nephropathy, respectively. The benefits of ACE-I, however, are tempered by their anti-erythropoietic effects and potential role in anemia. We conducted a retrospective study based on extraction of electronic medical records available through the Washington Veterans Affairs Medical Center. We compared hemoglobin levels of diabetic African-American and Caucasian patients on ACE-I or ARB, referred to the Hematology Section with a diagnosis of unexplained anemia within a 10-year span from January 1, 1998 to January 1, 2008. Additional sub-stratification analyses were performed on insulin dependence and renal function. Of the 102 African-Americans and 25 Caucasians evaluated, 60 African-Americans and 13 Caucasians were not anemic prior to initiation of ACE-I or ARB therapy. In this group, a greater decline from pretreatment hemoglobin levels were evident in African-Americans compared with Caucasians, with an average change in hemoglobin of −2.76 ± 1.34 g/dL compared with −2.04 ± 1.35 g/dL, respectively, though neither change was statistically significant. A greater decrease in hemoglobin levels was also evident depending on length of time on ACE-I therapy in African Americans. The average change in hemoglobin was −0.85 ± 1.87 g/dL at less than 5 years, −1.25 ± 1.55 g/dL at 5–10 years, and −3.15 ± 1.61 g/dL at 10–15 years after initiation of therapy. Limited data were available for Caucasians. Pearson correlation analyses also showed a weak positive correlation between decline in hemoglobin levels and decline in renal function. The average change in hemoglobin concentration after initiation of ACE-I or ARB therapy was greater in the subgroup of patients with estimated GFR less than 60cc/min in both African-Americans and Caucasians, with decrease of −1.85 ± 1.67g/dL and −1.60 ± 1.49g/dL, respectively. In African-Americans, decreases in hemoglobin were even greater for those patients with an estimated GFR less than 30cc/min, at 2.03 ± 2.19g/dL. Only one Caucasian patient had a GFR less than 30cc/min in our study. Greater decline in hemoglobin levels also correlated with insulin use even when renal function was accounted for, though this change was also not statistically significant. In diabetic African-Americans on ACE-I or ARB therapy, the change in hemoglobin was −2.03 ± 1.83 g/dL on insulin, compared with −1.64 ± 1.52 g/dL on no insulin. In diabetic Caucasians on ACE-I/ARB therapy, the change in hemoglobin was −1.38 ± 1.43 g/dL on insulin, compared with −1.11 ± 1.42 g/dL on no insulin. Our study is the first to include a large sub-population analysis of African-American diabetic patients to evaluate the effects of ACE-I and ARBs on the development or worsening of a hypoproliferative normocytic, normochromic anemia state. While results of this retrospective study were not statistically significant, due to small numbers, it does confirm ACE-I and ARB-mediated anemia may involve several downstream factors acting in concert and reinforces the need for additional large population studies.
Disclosures: No relevant conflicts of interest to declare.