Randomized Double-Blind Trial of Darbepoetin Alfa in Patients With Symptomatic Heart Failure and Anemia

Abstract

on behalf of the Study of Anemia in Heart Failure Trial (STAMINA-HeFT) GroupBackground-Substantial evidence suggests that anemia is an independent risk factor for worse outcomes in patients with heart failure (HF). The Study of Anemia in Heart Failure Trial (STAMINA-HeFT) is the largest multicenter, randomized, double-blind, placebo-controlled trial to date evaluating the effect of treating anemia in HF. Methods and Results-Patients (Nϭ319) with symptomatic HF, left ventricular ejection fraction Յ40%, and hemoglobin Ն9.0 g/dL and Յ12.5 g/dL were randomized (double-blind) to placebo (Nϭ157) or darbepoetin alfa (Nϭ162) subcutaneously every 2 weeks for 1 year (target hemoglobin, 14.0Ϯ1.0 g/dL). The primary end point was change from baseline to week 27 in treadmill exercise time. Secondary end points were change from baseline in New York Heart Association class and quality of life at week 27. An additional prespecified efficacy analysis included the time to death by any cause or first HF-related hospitalization by 1 year. At baseline, the median (interquartile range) hemoglobin was 11.4 (10.9, 12.0) g/dL. At week 27, darbepoetin alfa treatment increased median (interquartile range) hemoglobin by 1.8 (1.1, 2.5) g/dL (placebo, 0.3 [Ϫ0.2, 1.0] g/dL; PϽ0.001). Of the patients treated with darbepoetin alfa, 85% achieved 2 consecutive hemoglobin levels of 14.0Ϯ1.0 g/dL during the study and experienced a hemoglobin increase of Ն1.0 g/dL from baseline. By intent-to-treat analysis, darbepoetin alfa treatment did not significantly improve exercise duration, New York Heart Association class, or quality of life score compared with placebo. A nonsignificant trend was observed toward a lower risk of all-cause mortality or first HF hospitalization in darbepoetin alfa-treated patients compared with placebo (hazard ratio, 0.68; 95% CI, 0.43, 1.08; Pϭ0.10). Occurrences of adverse events were similar in both treatment groups. Conclusions-In this study of patients with symptomatic HF and anemia, treatment with darbepoetin alfa was not associated with significant clinical benefits. Darbepoetin alfa treatment was well tolerated and effectively raised hemoglobin. A trend of lower risk of morbidity and mortality was observed. (Circulation. 2008;117:526-535.)

Adaptive Servo-Ventilation Therapy Improves Long-Term Prognosis in Heart Failure Patients With Anemia and Sleep-Disordered Breathing

“…Although some studies using ESAs performed in single center trials showed improvement of NYHA functional class and echocardiographic data in CHF patients with anemia, 6,7) the latest multicenter randomized, double blind, placebo-controlled trial did not yield the expected results. 8,9) These findings might demonstrate that ESAs alone would be insufficient for improving the oxygenation of heart failure patients with anemia.…”

“…Although several reports demonstrated the benefit of ESAs in CHF patients who had declining NYHA functional classes or increasing contractions of the left ventricle, 6,7) a few reports did not reveal any definite clinical benefit of ESAs in CHF patients. 8,9) Hence, effective pharmacotherapy for CHF with anemia is still unclear.…”

The issue of anemic syndrome in CHF: a review of results from the RED-HF study and own data

“…Результаты другого мета-анализа (7 исследова-ний, 650 больных) также продемонстрировали безопас-ность использования рекомбинантного ЭПО (рЭПО) при ХСН [17]. Однако в исследовании STAMINA-HeFТ использование дарбопоэтина альфа не привело ни к повы-шению переносимости физической нагрузки, ни к умень-шению ФК ХСН, ни к улучшению качества жизни [18].…”

Clinical implications of iron deficiency/anemia in heart failure and approach to the treatment

“…Sin embargo, dos estudios controlados 29,30 , uno con poco más de 300 pacientes, y el otro con 2728 y 28 meses de seguimiento, no resultaron en diferencia significativa alguna entre el tratamiento con darbapoyetina alfa (eritropoyetina sintética de segunda generación) o placebo, además de la demostración del aumento de riesgo a sufrir eventos cerebrovasculares en este grupo de pacientes 31 . Con ellos se cierra el capítulo de la posible utilidad terapéutica de los AEE en IC.…”