Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia.
BACKGROUND
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.


RESULTS
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<0.001). Of the patients treated with darbepoetin alfa, 85% achieved 2 consecutive hemoglobin levels of 14.0+/-1.0 g/dL during the study and experienced a hemoglobin increase of > 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.


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.
Ghali
Jalal K
JK
Wayne State University, Detroit, Mich, USA. jghali@med.wayne.edu
Anand
Inder S
IS
Abraham
William T
WT
Fonarow
Gregg C
GC
Greenberg
Barry
B
Krum
Henry
H
Massie
Barry M
BM
Wasserman
Scott M
SM
Trotman
Marie-Louise
ML
Sun
Yan
Y
Knusel
Beat
B
Armstrong
Paul
P
D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000188:drug therapy*; D000068256:Darbepoetin alfa; D004311:Double-Blind Method; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017079:Exercise Tolerance; D005260:Female; D006333:Heart Failure / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D013318:Stroke Volume; D015996:Survival Rate
D006454:Hemoglobins; D004921:Erythropoietin; D000068256:Darbepoetin alfa