The effects of erythropoiesis stimulating therapy for anemia in chronic heart failure: A meta-analysis of randomized clinical trials

Background: Although anemia is common in chronic heart failure (CHF), the use of erythropoiesis stimulating agents (ESAs) in CHF patients remains controversial. In this meta-analysis, we sought to clarify the efficacy and safety of ESAs in anemic patients with CHF. Methods: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, the U.S. National Institutes of Health registry of clinical trials. We included 13 randomized clinical trials (RCTs) in the meta-analysis. The co-primary outcome was all-cause mortality and rehospitalization. The safety analysis outcome was thromboembolic events. Results: Preliminary analysis showed that ESA-treatment did not have any effect for all-cause mortality and rehospitalization. However, we revealed a significant small-study bias, and used the trim-and-fillmethod to reduce this bias. The summary effect of ESA-treatment was insignificant for all-cause mortality (risk ratio [RR] 0.91, 95% confidence interval [CI] 0.59-1.42, p = 0.69) and for rehospitalization (RR 0.91, 95% CI 0.67-1.23, p = 0.53). Regarding symptoms, ESA-treatment improved dyspnea (NYHA grade improvement: 1.63, 95% CI 0.65-2.62, p < 0.001) and quality-of-life measured by subjective questionnaires. However, in safety analysis, ESAs increased the over-all risk for thromboembolic events (RR 1.28, 95% CI 1.03-1.58, p = 0.026), however, no specific increase was observed in severe thromboembolic events. Subgroup analysis showed no difference in ESA-treatment according to the type of ESAs (darbepoetin vs. erythropoietin) and between studies of different follow-up durations (<6 months or >= 6 months). Conclusion: Among CHF patients with anemia, ESA-treatment has a neutral effect on all-cause mortality and rehospitalization and improves symptoms, but has harmful effects on thromboembolic events. (C) 2016 Elsevier Ireland Ltd. All rights reserved.