Erythropoiesis-stimulating agents to reduce heart failure hospitalization: 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 hospitalization remains unclear.

Methods and results: A pre-registered systematic search was performed of randomized controlled trials in adults with CHF and anaemia, comparing any ESA at any dose versus placebo or no treatment.

Fourteen trials were included with 3128 participants, with moderate quality of evidence for most outcomes and variable risk of bias. Meta-analysis during 5604 person-years of follow-up demonstrated no significant difference in first CHF hospitalization comparing ESAs with control: Peto odds ratio (OR) 0.93, 95% CI 0.78-1.10, P = .37; trial heterogeneity I² = 36%. ESAs significantly reduced total CHF hospitalization with 622 events/2698 person-years, compared with 761/2914 person-years for control: incidence rate ratio 0.81, 95% CI 0.73 to 0.90, P < .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 = .88; I² = 35%) or incident adverse events. Patients randomized to ESAs increased their haemoglobin level [mean difference (MD) 1.6 g/dL compared with control, 95% CI 1.6-1.7, P < .001] and exercise tolerance (MD 69 metres, 95% CI 17-122, P = .009), with lower NYHA class on follow-up (MD -0.73 class, 95% CI -1.11 to -0.36, P < .001).

Conclusion: ESA treatment in patients with CHF and mild anaemia can reduce recurrent CHF hospitalization 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.