Erythropoietin improves anemia exercise tolerance and renal function and reduces B-type natriuretic peptide and hospitalization in patients with heart failure and anemia.
BACKGROUND
Anemia is now recognized as being a common finding in CHF 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 (s.c.) beta-EPO in combination with iron have either been uncontrolled or case-controlled studies. We report a randomized, double-blind, placebo-controlled study of the combination of s.c. EPO and oral iron versus oral iron alone in patients with anemia and resistant CHF.


OBJECTIVE
The present study examines, in patients with advanced congestive heart failure (CHF) and anemia, the effects of beta-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] <11 g/dL) were studied. They were randomized to receive, in a double-blind fashion, either (a) (group A, the treatment group, 20 patients) s.c. 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 s.c. 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 same 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 (VO2) from 12.8 +/- 2.8 to 15.1 +/- 2.8 mL/kg per minute (<.05); and the VO2 at 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 natriuretic peptide levels from 568 +/- 320 to 271 +/- 120 pg/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 natriuretic peptide levels and reduces the need for hospitalization.
Palazzuoli
Alberto
A
Cardiology Section, Department of Internal Medicine and Metabolic Diseases, Le Scotte Hospital, University of Siena, Siena, Italy. palazzuoli2@unisi.it
Silverberg
Donald
D
Iovine
Francesca
F
Capobianco
Stefano
S
Giannotti
Giovanna
G
Calabrò
Anna
A
Campagna
Stella Maria
SM
Nuti
Ranuccio
R
D000368:Aged; D000369:Aged, 80 and over; D015308:Anaerobic Threshold; D000740:Anemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D004921:Erythropoietin / Q000627:therapeutic use*; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications* / Q000503:physiopathology; D006454:Hemoglobins / Q000378:metabolism; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010101:Oxygen Consumption; D010807:Physical Endurance / Q000187:drug effects*; D012720:Severity of Illness Index
D006454:Hemoglobins; D004921:Erythropoietin; D020097:Natriuretic Peptide, Brain; D003404:Creatinine