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CLINICAL RESEARCH: CLINICAL TRIALS

Effect of Darbepoetin Alfa on Exercise Tolerance in Anemic Patients With Symptomatic Chronic Heart Failure

A Randomized, Double-Blind, Placebo-Controlled Trial

Piotr Ponikowski, MD, PhD^_*, Stefan D. Anker, MD, PhD^,, Joanna Szachniewicz, MD^_*, Darlington Okonko, BSc, MRCP, Mark Ledwidge, PhD, Robert Zymlinski, MD^_*, Enda Ryan, MRCP, Scott M. Wasserman, MD^||, Nigel Baker, MSc^||, Dylan Rosser, BSc^||, Stuart D. Rosen, MD, Philip A. Poole-Wilson, MD, Waldemar Banasiak, MD, PhD^_*, Andrew J.S. Coats, DM^¶ and Ken McDonald, MD^,_*

^_* Cardiac Department, Military Hospital, Wroclaw, Poland
Clinical Cardiology, National Heart and Lung Institute, Imperial College London, London, England
Division of Applied Cachexia Research, Department of Cardiology, Charité Campus Virchow-Klinikum, Berlin, Germany
Department of Cardiology, St. Vincent's University Hospital, Elm Park, Dublin, Ireland
^|| Amgen Limited, 240 Cambridge Science Park, Cambridge, England
^¶ Faculty of Medicine, University of Sydney, Sydney, Australia

Manuscript received June 14, 2006; revised manuscript received August 30, 2006, accepted September 11, 2006.

^_* Reprint requests and correspondence: Dr. Ken McDonald, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. (Email: kenneth.mcdonald{at}ucd.ie).

OBJECTIVES: 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 9.0 to 12.0 g/dl) received subcutaneous placebo (n = 22) or darbepoetin alfa (n = 19) at a starting dose of 0.75 µg/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 VO ₂ (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 VO ₂ (p = 0.40), 45 ml/min (–35 to 127) for absolute peak VO ₂ (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 VO ₂ 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 [ClinicalTrials.gov] ).

Abbreviations and Acronyms   BNP = brain natriuretic peptide concentration   CHF = chronic heart failure   CI = confidence interval   ESP = erythropoiesis-stimulating protein   KCCQ = Kansas City Cardiomyopathy Questionnaire   LVEF = left ventricular ejection fraction   MLHFQ = Minnesota Living With Heart Failure Questionnaire   NYHA = New York Heart Association   PGA = Patient's Global Assessment of Change   VO 2 = oxygen uptake per kilogram body weight

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