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

• Published in: Circulation (New York, N.Y.) N.Y.), 2008-01, Vol.117 (4), p.526-535
• Main Authors: GHALI, Jalal K, ANAND, Inder S, KNUSEL, Beat, ARMSTRONG, Paul, ABRAHAM, William T, FONAROW, Gregg C, GREENBERG, Barry, KRUM, Henry, MASSIE, Barry M, WASSERMAN, Scott M, TROTMAN, Marie-Louise, YAN SUN
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Anemia - drug therapy; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular system; Darbepoetin alfa; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Double-Blind Method; Erythropoietin - administration & dosage; Erythropoietin - analogs & derivatives; Exercise Tolerance; Female; Heart Failure - complications; Heart Failure - drug therapy; Heart Failure - mortality; Hemoglobins - analysis; Humans; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Quality of Life; Stroke Volume; Survival Rate; Vasodilator agents. Cerebral vasodilators
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.107.698514

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. Patients (N=319) with symptomatic HF, left ventricular ejection fraction < or = 40%, and hemoglobin > or = 9.0 g/dL and < or = 12.5 g/dL were randomized (double-blind) to placebo (N=157) or darbepoetin alfa (N=162) subcutaneously every 2 weeks for 1 year (target hemoglobin, 14.0+/-1.0 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 [-0.2, 1.0] g/dL; P or = 1.0 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; P=0.10). Occurrences of adverse events were similar in both treatment groups. 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.