Anaemia is common in patients with systolic heart failure and is associated with lower functional capacity, worse quality of life, and higher rates of hospitalization and death. The cause of anaemia in these patients is often unclear but may be related to an absolute or relative deficiency of, or resistance to, erythropoietin. In this study Swedberg et al. evaluated the effects of erythropoietin replacement with darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anaemia.
In a multi-centre international randomized, double-blind trial, 2278 patients with systolic heart failure and mild-to-moderate anaemia (haemoglobin level, 9.0 to 12.0 g/dL) and no evidence of iron deficiency were randomised to receive either darbepoetin alfa (to achieve a haemoglobin target of 13 g/dL) or placebo. The primary outcome was a composite of death from any cause or hospitalization for worsening heart failure.
The primary outcome occurred in 576 of 1136 patients (50.7%) in the darbepoetin group and 565 of 1142 patients (49.5%) in the placebo group (HR in the darbepoetin group, 1.01; 95% CI, 0.90 to 1.13; P=0.87). There was no significant between-group difference in any of the secondary outcomes which included death, hospitalisation and a quality of life index. The neutral effect of darbepoetin was also consistent across all prespecified subgroups. Looking at the safety end-points, there was no difference in fatal or nonfatal stroke which occurred in 42 patients (3.7%) in the darbepoetin group and 31 patients (2.7%) in the placebo group (P=0.23) but thromboembolic events were significantly increased in the darbepoetin group (153 patients (13.5%) vs. 114 patients (10.0%) (P=0.01)).
In this large randomised trial, treatment with darbepoetin alfa did not improve clinical outcomes in patients with systolic heart failure and mild-to-moderate anaemia.
- Swedberg K, Young JB, Anand IS, Cheng S, Desai AS, Diaz R, Maggioni AP, McMurray JJ, O’Connor C, Pfeffer MA, Solomon SD, Sun Y, Tendera M, van Veldhuisen DJ. Treatment of Anemia with Darbepoetin Alfa in Systolic Heart Failure. N Engl J Med. 2013;368:2010-2019.