Erythropoietin improves anemia exercise tolerance and renal function and reduces B-type natriuretic pepticle and hospitalization in patients with heart failure and anemia

Background Anemia is now recognized as being a common finding in CHIF and is associated with increased mortality and morbidity. However, it is uncertain whether the anemia is actually causing the worse prognosis or is merely a marker of more severe cardiac disease. Previous intervention studies with subcutaneous (sc) beta-EPO in combination with iron have either been uncontrolled or case-controlled studies. We report a randomized, double-blind, placebo-control led study of the combination of sc EPO and oral iron versus oral iron alone in patients with anemia and resistant CHF. Objectives The present study examines, in patients with advanced congestive heart failure (CHF) and anemia, the effects of t-erythropoietin (EPO) and oral iron on the anemia and on cardiac and renal functional parameters. Methods Forty consecutive subjects with moderate to severe CHF and anemia (hemoglobin [Hb] < 119/dL) were studied. They were randomized to receive, in a double-blind fashion, either (a) (group A, the treatment group, 20 patients) sc beta-EPO for 3 months twice weekly, in addition to daily oral iron, or (b) (group B, the placebo group, 20 patients) normal saline in sc injections and daily oral iron. Two patients in group B were eventually excluded because of a fall of Hb < 8 g/dL requiring transfusion, leaving 18 patients in group B. After the 3-months study, the group A patients were maintained on the some treatment for an additional 9 months, whereas in Group B, the placebo and oral iron were stopped. Results In group A, after a mean of 3.5 +/- 0.8 months of treatment, there was a significant increase in Hb from 10.4 +/- 0.6 to 12.4 +/- 0.8 g/dL (P < .01); a significant improvement in New York Heart Association functional class from 3.5 0.6 to 2.8 +/- 0.5 (P < .05); a longer endurance time on exercise testing, from 5.8 +/- 2.2 to 7.8 +/- 2.5 minutes (P < .01); a greater distance walked on exercise testing, from 278 55 to 356 88 meters (P < .01); a significant increase in the peak oxygen consumption (V.O-2) from 12.8 +/- 2.8 to 15.1 +/- 2.8 mL/kg per minute (<.05); and the V.O-2 of the anaerobic threshold, from 9.2 +/- 2.0 to 13.2 +/- 3.6 mL/kg minute (P <.01). There was also a significant fall in plasma B-type notriuretic peptide levels from 568 +/- 320 to 271 +/- 120 mu g/mL (P < .01), a significant reduction in serum creatinine (P < .01), and an increase in estimated creatinine clearance (P < .05). In group B, there were no significant changes in any of the above parameters over the study period. At the end of the 1-year study, the Hb was still higher in group A than group B, and the rate of hospital admissions/patients over the year averaged 0.8 +/- 0.2 in group A and 1.7 +/- 0.8 in group B (P < .01). Conclusions in anemic CHF patients, correction of anemia with EPO and oral iron leads to improvement in New York Heart Association status, measured exercise endurance, oxygen use during exercise, renal function and plasma B-type notriuretic peptide levels and reduces the need for hospitalization.