RESUMO
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) Assuntos
Anemia/tratamento farmacológico
, Eritropoetina/análogos & derivados
, Insuficiência Cardíaca/complicações
, Hematínicos/administração & dosagem
, Administração Cutânea
, Idoso
, Anemia/sangue
, Anemia/complicações
, Doença Crônica
, Darbepoetina alfa
, Relação Dose-Resposta a Droga
, Método Duplo-Cego
, Eritropoetina/administração & dosagem
, Eritropoetina/efeitos adversos
, Teste de Esforço
, Tolerância ao Exercício
, Feminino
, Hematínicos/efeitos adversos
, Hemoglobinas/metabolismo
, Humanos
, Masculino
, Satisfação do Paciente
, Volume Sistólico
, Inquéritos e Questionários
, Resultado do Tratamento
RESUMO
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 > 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).
Assuntos
Anemia/etiologia , Anemia/fisiopatologia , Eritropoetina/análogos & derivados , Tolerância ao Exercício/efeitos dos fármacos , Insuficiência Cardíaca/complicações , Hematínicos/uso terapêutico , Atividades Cotidianas , Idoso , Anemia/terapia , Peso Corporal , Darbepoetina alfa , Método Duplo-Cego , Eritropoetina/uso terapêutico , Teste de Esforço/efeitos dos fármacos , Feminino , Hemoglobinas/efeitos dos fármacos , Hospitalização , Humanos , Injeções Subcutâneas , Masculino , Peptídeo Natriurético Encefálico/sangue , Consumo de Oxigênio/efeitos dos fármacos , Qualidade de Vida , Resultado do TratamentoRESUMO
In patients with chronic heart failure (CHF), anemia is associated with more severe symptoms and worse prognosis. Erythropoiesis-stimulating proteins (ESPs) increase hemoglobin and may be of therapeutic benefit. We investigated the pharmacokinetics and pharmacodynamics of the long-acting ESP, darbepoetin alfa, administered on 2 occasions 1 month apart to 30 healthy subjects and 33 patients with symptomatic CHF and anemia (hemoglobinAssuntos
Anemia/tratamento farmacológico
, Baixo Débito Cardíaco/tratamento farmacológico
, Eritropoetina/análogos & derivados
, Idoso
, Anemia/sangue
, Anemia/complicações
, Disponibilidade Biológica
, Baixo Débito Cardíaco/sangue
, Baixo Débito Cardíaco/complicações
, Doença Crônica
, Estudos Cross-Over
, Darbepoetina alfa
, Método Duplo-Cego
, Esquema de Medicação
, Eritropoetina/administração & dosagem
, Eritropoetina/farmacocinética
, Eritropoetina/farmacologia
, Eritropoetina/uso terapêutico
, Feminino
, Hemoglobinas/análise
, Humanos
, Injeções Intravenosas
, Injeções Subcutâneas
, Masculino
, Pessoa de Meia-Idade