Erythropoiesis-stimulating agents to reduce heart failure hospitalisation: A systematic review and meta-analysis

Aims Anaemia is common in patients with chronic heart failure (CHF), worsening functional status and prognosis. The role of erythropoiesis-stimulating agents (ESAs) to reduce hospitalisation remains unclear. Methods and results A pre-registered systematic search was performed of randomised controlled trials in adults with CHF and anaemia, comparing any ESA at any dose versus placebo or no treatment. Fourteen trials were included with 3,128 participants, with moderate quality of evidence for most outcomes and variable risk of bias. Meta-analysis during 5,604 person-years of follow-up demonstrated no significant difference in first CHF hospitalisation comparing ESAs with control: Peto odds ratio (OR) 0.93, 95% CI 0.78-1.10, p=0.37; trial heterogeneity I2=36%. ESAs significantly reduced total CHF hospitalisation with 622 events/2,698 person-years, compared to 761/2,914 person-years for control: incidence rate ratio 0.81, 95% CI 0.73 to 0.90, p<0.001; no heterogeneity between trials, I2=0%. There were no significant differences between treatment groups for all-cause mortality (OR 1.01, 95% CI 0.86-1.18, p= 0.88; I2=35%) or incident adverse events. Patients randomised to ESAs increased their haemoglobin level (mean difference [MD] 1.6 g/dL compared to control, 95% CI 1.6-1.7, p<0.001) and exercise tolerance (MD 69 metres, 95% CI 17-122, p=0.009), with lower NYHA class on follow-up (MD −0.73 class, 95% CI -1.11 to -0.36, p<0.001). Conclusion ESA treatment in patients with CHF and mild anaemia can reduce recurrent CHF hospitalisation and improve functional capacity, without any impact on adverse events. Including ESAs in CHF management could be considered in patients with anaemia at high risk of recurrent hospital admissions.