J Am Coll Cardiol, 2007; 49:753-762, doi:10.1016/j.jacc.2006.11.024 (Published online 6 February 2007). © 2007 by the American College of Cardiology Foundation

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: j.jacc.2006.11.024v1 49/7/753    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (42) Citing Articles via Google Scholar Google Scholar Articles by Ponikowski, P. Articles by McDonald, K. Search for Related Content PubMed PubMed Citation Articles by Ponikowski, P. Articles by McDonald, K. Related Collections Related Article

CLINICAL RESEARCH: CLINICAL TRIAL

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^_*,3,6, Stefan D. Anker, MD, PhD^,,1,3,4,6, Joanna Szachniewicz, MD^_*, Darlington Okonko, BSc, MRCP^,2, Mark Ledwidge, PhD, Robert Zymlinski, MD^_*, Enda Ryan, MRCP, Scott M. Wasserman, MD^||, Nigel Baker, MSc^||,5, Dylan Rosser, BSc^||,5, Stuart D. Rosen, MD, Philip A. Poole-Wilson, MD, Waldemar Banasiak, MD, PhD^_*, Andrew J.S. Coats, DM^¶,3,4 and Ken McDonald, MD^,3,_*

^_* 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

Related Article

Anemia in Chronic Heart Failure: Should We Treat It and How?

Michel Komajda
J. Am. Coll. Cardiol. 2007 49: 763-764. [Full Text] [PDF]

This article has been cited by other articles:

				M. Klapholz, W. T. Abraham, J. K. Ghali, P. Ponikowski, S. D. Anker, B. Knusel, Y. Sun, S. M. Wasserman, and D. J. van Veldhuisen The safety and tolerability of darbepoetin alfa in patients with anaemia and symptomatic heart failure Eur J Heart Fail, November 1, 2009; 11(11): 1071 - 1077. [Abstract] [Full Text] [PDF]

				P van der Meer, H F Groenveld, J L Januzzi Jr, and D J van Veldhuisen Erythropoietin treatment in patients with chronic heart failure: a meta-analysis Heart, August 15, 2009; 95(16): 1309 - 1314. [Abstract] [Full Text] [PDF]

				J. J.V. McMurray, I. S. Anand, R. Diaz, A. P. Maggioni, C. O'Connor, M. A. Pfeffer, K. R. Polu, S. D. Solomon, Y. Sun, K. Swedberg, et al. Design of the Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF): a Phase III, anaemia correction, morbidity-mortality trial Eur J Heart Fail, August 1, 2009; 11(8): 795 - 801. [Abstract] [Full Text] [PDF]

				B P Geisler, R M van Dam, G S Gazelle, and A Goehler Risk of bias in meta-analysis on erythropoietin-stimulating agents in heart failure Heart, August 1, 2009; 95(15): 1278 - 1279. [Full Text] [PDF]

				S. D. Anker, A. Voors, D. Okonko, A. L. Clark, M. K. James, S. von Haehling, J. Kjekshus, P. Ponikowski, K. Dickstein, and for the OPTIMAAL Investigators Prevalence, incidence, and prognostic value of anaemia in patients after an acute myocardial infarction: data from the OPTIMAAL trial Eur. Heart J., June 1, 2009; 30(11): 1331 - 1339. [Abstract] [Full Text] [PDF]

				E. Gao and W. J. Koch Is erythropoietin behind maladaptive anemic heart failure? Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H559 - H560. [Full Text] [PDF]

				A. Kazory and E. A. Ross Anemia: the point of convergence or divergence for kidney disease and heart failure? J. Am. Coll. Cardiol., February 24, 2009; 53(8): 639 - 647. [Abstract] [Full Text] [PDF]

				E. D. Pagourelias, C. Koumaras, A. I. Kakafika, K. Tziomalos, P. G. Zorou, V. G. Athyros, and A. Karagiannis Cardiorenal Anemia Syndrome: Do Erythropoietin and Iron Therapy Have a Place in the Treatment of Heart Failure? Angiology, February 1, 2009; 60(1): 74 - 81. [Abstract] [PDF]

				S. D. Anker and R. Toto Future perspectives on treatment with erythropoiesis-stimulating agents in high-risk patients NDT Plus, January 1, 2009; 2(suppl_1): i3 - i8. [Abstract] [Full Text] [PDF]

				D. S. Silverberg, D. Wexler, A. Iaina, and D. Schwartz The Role of Correction of Anemia in Patients With Congestive Heart Failure Associated with Chronic Kidney Failure Journal of Pharmacy Practice, December 1, 2008; 21(6): 420 - 423. [Abstract] [PDF]

				S. Rastogi, M. Imai, V. G. Sharov, S. Mishra, and H. N. Sabbah Darbepoetin-{alpha} prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2475 - H2482. [Abstract] [Full Text] [PDF]

				Authors/Task Force Members, K. Dickstein, A. Cohen-Solal, G. Filippatos, J. J.V. McMurray, P. Ponikowski, P. A. Poole-Wilson, A. Stromberg, D. J. van Veldhuisen, D. Atar, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM) Eur. Heart J., October 1, 2008; 29(19): 2388 - 2442. [Full Text] [PDF]

				K. Dickstein, A. Cohen-Solal, G. Filippatos, J. J.V. McMurray, P. Ponikowski, P. A. Poole-Wilson, A. Stromberg, D. J. van Veldhuisen, D. Atar, A. W. Hoes, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM) Eur J Heart Fail, October 1, 2008; 10(10): 933 - 989. [Full Text] [PDF]

				D. S. Silverberg, D. Wexlerb, A. Iaina, and D. Schwartz The role of correction of anaemia in patients with congestive heart failure: A short review Eur J Heart Fail, September 1, 2008; 10(9): 819 - 823. [Abstract] [Full Text] [PDF]

				K. S. Courneya, L. W. Jones, C. J. Peddle, C. M. Sellar, T. Reiman, A. A. Joy, N. Chua, L. Tkachuk, and J. R. Mackey Effects of Aerobic Exercise Training in Anemic Cancer Patients Receiving Darbepoetin Alfa: A Randomized Controlled Trial Oncologist, September 1, 2008; 13(9): 1012 - 1020. [Abstract] [Full Text] [PDF]

				I. S. Anand Anemia and Chronic Heart Failure: Implications and Treatment Options J. Am. Coll. Cardiol., August 12, 2008; 52(7): 501 - 511. [Abstract] [Full Text] [PDF]

				A. Kazory and E. A. Ross Contemporary Trends in the Pharmacological and Extracorporeal Management of Heart Failure: A Nephrologic Perspective Circulation, February 19, 2008; 117(7): 975 - 983. [Abstract] [Full Text] [PDF]

				J. K. Ghali, I. S. Anand, W. T. Abraham, G. C. Fonarow, B. Greenberg, H. Krum, B. M. Massie, S. M. Wasserman, M.-L. Trotman, Y. Sun, et al. Randomized Double-Blind Trial of Darbepoetin Alfa in Patients With Symptomatic Heart Failure and Anemia Circulation, January 29, 2008; 117(4): 526 - 535. [Abstract] [Full Text] [PDF]

				J. E. Toblli, A. Lombrana, P. Duarte, and F. Di Gennaro Intravenous Iron Reduces NT-Pro-Brain Natriuretic Peptide in Anemic Patients With Chronic Heart Failure and Renal Insufficiency J. Am. Coll. Cardiol., October 23, 2007; 50(17): 1657 - 1665. [Abstract] [Full Text] [PDF]

				G. S. Francis and A. Kanderian Anemia and Heart Failure: A New Pathway? J. Am. Coll. Cardiol., October 23, 2007; 50(17): 1666 - 1667. [Full Text] [PDF]

				D. J. van Veldhuisen, K. Dickstein, A. Cohen-Solal, D. J.A. Lok, S. M. Wasserman, N. Baker, D. Rosser, J. G.F. Cleland, and P. Ponikowski Randomized, double-blind, placebo-controlled study to evaluate the effect of two dosing regimens of darbepoetin alfa in patients with heart failure and anaemia Eur. Heart J., September 2, 2007; 28(18): 2208 - 2216. [Abstract] [Full Text] [PDF]

				Darbepoetin Alfa Tested in Anemic HF Patients Journal Watch Cardiology, March 6, 2007; 2007(306): 5 - 5. [Full Text]

				M. Komajda Anemia in Chronic Heart Failure: Should We Treat It and How? J. Am. Coll. Cardiol., February 20, 2007; 49(7): 763 - 764. [Full Text] [PDF]