Effect of darbepoetin alfa on exercise tolerance in anemic patients with symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled trial.
OBJECTIVE
This study sought to investigate whether darbepoetin alfa, an erythropoiesis-stimulating protein (ESP), improves exercise capacity in patients with symptomatic chronic heart failure (CHF) and anemia.


BACKGROUND
Anemia is common in patients with CHF.


METHODS
In a multicenter, randomized, double-blind, placebo-controlled study, CHF patients with anemia (hemoglobin > or =9.0 to < or =12.0 g/dl) received subcutaneous placebo (n = 22) or darbepoetin alfa (n = 19) at a starting dose of 0.75 microg/kg every 2 weeks for 26 weeks. The primary end point was change in exercise tolerance from baseline to week 27 as measured by peak oxygen uptake (ml/min/kg body weight). Other end points included changes in absolute peak VO2 (ml/min), exercise duration, and health-related quality of life.


RESULTS
Differences (95% confidence interval) in mean changes from baseline to week 27 between treatment groups were 1.5 g/dl (0.5 to 2.4) for hemoglobin concentration (p = 0.005), 0.5 ml/kg/min (-0.7 to 1.7) for peak VO2 (p = 0.40), 45 ml/min (-35 to 127) for absolute peak VO2 (p = 0.27), and 108 s (-11 to 228) for exercise duration (p = 0.075). Patients receiving darbepoetin alfa compared with placebo had an improvement in self-reported Patient's Global Assessment of Change (79% vs. 41%, p = 0.01) but no significant differences in the Kansas City Cardiomyopathy and Minnesota Living with Heart Failure Questionnaire scores. Darbepoetin alfa was well tolerated.


CONCLUSIONS
In patients with symptomatic CHF and anemia, darbepoetin alfa increased and maintained hemoglobin concentrations and improved health-related quality of life. A trend toward increased exercise time but not peak VO2 was observed. (Impact of Darbepoetin Alfa on Exercise Tolerance and Left Ventricular Structure in Subjects With Symptomatic Congestive Heart Failure (CHF) and Anemia; http://clinicaltrials.gov/ct/show/NCT00117234?order = 1; NCT00117234).
Ponikowski
Piotr
P
Cardiac Department, Military Hospital, Wroclaw, Poland.
Anker
Stefan D
SD
Szachniewicz
Joanna
J
Okonko
Darlington
D
Ledwidge
Mark
M
Zymlinski
Robert
R
Ryan
Enda
E
Wasserman
Scott M
SM
Baker
Nigel
N
Rosser
Dylan
D
Rosen
Stuart D
SD
Poole-Wilson
Philip A
PA
Banasiak
Waldemar
W
Coats
Andrew J S
AJ
McDonald
Ken
K
D000203:Activities of Daily Living; D000368:Aged; D000740:Anemia / Q000209:etiology* / Q000503:physiopathology* / Q000628:therapy; D001835:Body Weight; D000068256:Darbepoetin alfa; D004311:Double-Blind Method; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005080:Exercise Test / Q000187:drug effects; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006333:Heart Failure / Q000150:complications*; D006397:Hematinics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000187:drug effects; D006760:Hospitalization; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D011788:Quality of Life; D016896:Treatment Outcome
D006397:Hematinics; D006454:Hemoglobins; D004921:Erythropoietin; D020097:Natriuretic Peptide, Brain; D000068256:Darbepoetin alfa