PMID- 17681958
OWN - NLM
STAT- MEDLINE
DCOM- 20080403
LR  - 20151119
IS  - 0195-668X (Print)
IS  - 0195-668X (Linking)
VI  - 28
IP  - 18
DP  - 2007 Sep
TI  - Randomized, double-blind, placebo-controlled study to evaluate the effect of two 
      dosing regimens of darbepoetin alfa in patients with heart failure and anaemia.
PG  - 2208-16
AB  - AIMS: Anaemia is common in chronic heart failure (CHF) and associated with worse 
      outcome. This randomized, double-blind, placebo-controlled study evaluated the 
      effect of two darbepoetin alfa dosing regimens on haemoglobin (Hb) rate of rise 
      and clinical effects in patients with CHF and anaemia. METHODS AND RESULTS: 
      Patients with CHF (>or=3 months), left ventricular ejection fraction (LVEF) <or= 
      40%, and Hb 9.0 to 12.5 g/dL received darbepoetin alfa subcutaneously every 2 
      weeks for 26 weeks at a starting weight-adjusted dose of 0.75 mcg/kg (n = 56) or 
      a fixed dose of 50 mcg (n = 54), or placebo (n = 55), to gradually achieve and 
      maintain a target Hb of 14.0 +/- 1.0 g/dL. Endpoints included rate of Hb rise per 
      week during titration, safety, and changes in 6 min walk distance, New York Heart 
      Association (NYHA) class, LVEF, and quality of life. Most subjects were NYHA 
      class II-III. Mean (SD) age was 71 (11) years, LVEF was 28 (9), and Hb 11.5 (0.7) 
      g/dL. Rate of Hb rise was equivalent between darbepoetin alfa weight-based (+1.87 
      +/- 1.36 g/dL) and fixed dosing (+1.64 +/- 0.98 g/dL) groups, vs. + 0.07 +/- 1.08 
      g/dL in the placebo group. Mean Hb concentrations by week 27 were 13.4 and 13.2 
      g/dL, in the weight-based and fixed dosing groups, respectively. There were 
      non-significant improvements in the combined darbepoetin alfa group vs. placebo 
      for 6 min walk distance (P = 0.074) and Patient's Global Assessment score (P = 
      0.057). There was a significant improvement in Kansas City Cardiomyopathy 
      Questionnaire total symptom score (8.2 vs. 1.5 points; P = 0.027) but no change 
      in NYHA class, LVEF, and Minnesota Living With Heart Failure Questionnaire score. 
      Six treatment-unrelated deaths occurred in the 110 darbepoetin alfa treated 
      patients, and none in the 55 placebo treated patients. Other adverse events were 
      similar between groups. CONCLUSION: In this study of patients with CHF and 
      anaemia, treatment with darbepoetin alfa raised Hb using different dosing 
      regimens. Darbepoetin alfa improved some quality of life indices, but its safety 
      requires further exploration. Larger trials are needed to determine the effects 
      on long-term morbidity and mortality.
FAU - van Veldhuisen, Dirk J
AU  - van Veldhuisen DJ
AD  - Department of Cardiology, University Medical Center Groningen, University of 
      Groningen, The Netherlands. d.j.van.veldhuisen@thorax.umcg.nl
FAU - Dickstein, Kenneth
AU  - Dickstein K
FAU - Cohen-Solal, Alain
AU  - Cohen-Solal A
FAU - Lok, Dirk J A
AU  - Lok DJ
FAU - Wasserman, Scott M
AU  - Wasserman SM
FAU - Baker, Nigel
AU  - Baker N
FAU - Rosser, Dylan
AU  - Rosser D
FAU - Cleland, John G F
AU  - Cleland JG
FAU - Ponikowski, Piotr
AU  - Ponikowski P
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20070806
PL  - England
TA  - Eur Heart J
JT  - European heart journal
JID - 8006263
RN  - 0 (Hematinics)
RN  - 0 (Hemoglobins)
RN  - 11096-26-7 (Erythropoietin)
RN  - 15UQ94PT4P (Darbepoetin alfa)
SB  - IM
CIN - Eur Heart J. 2007 Sep;28(18):2185-7. PMID: 17704094
CIN - Eur Heart J. 2008 Feb;29(4):565-6; author reply 566-7. PMID: 18192702
MH  - Administration, Cutaneous
MH  - Aged
MH  - Anemia/blood/complications/*drug therapy
MH  - Chronic Disease
MH  - Darbepoetin alfa
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Erythropoietin/administration & dosage/adverse effects/*analogs & derivatives
MH  - Exercise Test
MH  - Exercise Tolerance
MH  - Female
MH  - Heart Failure/*complications
MH  - Hematinics/*administration & dosage/adverse effects
MH  - Hemoglobins/metabolism
MH  - Humans
MH  - Male
MH  - Patient Satisfaction
MH  - Stroke Volume
MH  - Surveys and Questionnaires
MH  - Treatment Outcome
EDAT- 2007/08/08 09:00
MHDA- 2008/04/04 09:00
CRDT- 2007/08/08 09:00
PHST- 2007/08/08 09:00 [pubmed]
PHST- 2008/04/04 09:00 [medline]
PHST- 2007/08/08 09:00 [entrez]
AID - ehm328 [pii]
AID - 10.1093/eurheartj/ehm328 [doi]
PST - ppublish
SO  - Eur Heart J. 2007 Sep;28(18):2208-16. doi: 10.1093/eurheartj/ehm328. Epub 2007 
      Aug 6.