Erythropoiesis-stimulating agents to reduce heart failure hospitalization: a systematic review and meta-analysis
Clinical Snapshot
PICO Framework
| P — Population | Adults with chronic heart failure and anaemia |
| I — Intervention | Erythropoiesis-stimulating agents (ESAs) at any dose |
| C — Comparator | Placebo or no treatment |
| O — Outcomes | Primary: CHF hospitalization; Secondary: mortality, adverse events, haemoglobin levels, exercise tolerance, NYHA class |
Bottom Line
This meta-analysis of 14 RCTs (3128 participants) found that erythropoiesis-stimulating agents in chronic heart failure patients with anaemia reduce recurrent hospitalizations (19% relative reduction) and improve functional capacity, but do not prevent first hospitalizations or reduce mortality. The evidence quality is moderate with low heterogeneity between studies. ESAs increased haemoglobin by 1.6 g/dL and improved exercise tolerance by 69 metres. While no safety signals emerged, the mixed efficacy results and moderate evidence quality suggest ESAs should be considered selectively in anaemic CHF patients with high rehospitalization risk, after addressing reversible causes of anaemia. Australian clinicians should consider PBS restrictions and ensure appropriate patient selection and monitoring protocols.
Key Findings
P Value: P < 0.001 for total CHF hospitalization
Effect Size: Significant reduction in total CHF hospitalization (IRR 0.81, 95% CI 0.73-0.90, P < 0.001)
Primary Outcome: No significant reduction in first CHF hospitalization (Peto OR 0.93, 95% CI 0.78-1.10, P = 0.37)
Nnt Or Sensitivity: Number needed to treat approximately 11 patients to prevent one recurrent hospitalization based on event rates
Confidence Interval: 95% CI 0.73-0.90 for total hospitalization reduction
Clinical Application
ESAs available but require careful patient selection, monitoring, and consideration of cost-effectiveness ESAs available on PBS with Authority Required prescriptions for specific indications; RACGP guidelines emphasise treating underlying causes of anaemia first CHF patients with mild anaemia at high risk of recurrent hospital admissions
Abstract
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.
References
- 1.Bunting, K. V., Tica, O., Champsi, A., Perrett, M., von Lueder, T. G., van Veldhuisen, D. J., Flather, M. D., & Kotecha, D. (2026). Erythropoiesis-stimulating agents to reduce heart failure hospitalization: a systematic review and meta-analysis. European Journal of Heart Failure. https://doi.org/10.1093/ejhf/xuaf012
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