Are there any randomized trials investigating intravenous iron therapy in patients with sepsis or acute coronary syndrome?

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Last updated: February 20, 2026 • View editorial policy

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Trials of Intravenous Iron in Sepsis and Acute Coronary Syndrome

There are no randomized trials specifically investigating intravenous iron therapy in patients with active sepsis, and septic patients were explicitly excluded from critical care iron trials. 1 For acute coronary syndrome, observational data exist showing iron deficiency predicts worse outcomes, but no randomized trials have tested intravenous iron as a therapeutic intervention in this population. 2

Evidence in Sepsis

Exclusion from Critical Care Trials

  • The majority of studies evaluating intravenous iron in critical care patients specifically excluded septic patients from enrollment. 1
  • Included critical care populations were primarily trauma or postoperative patients, not those with active infection. 1
  • A 2020 guideline on anemia management in critical care explicitly notes this evidence gap, stating trials "excluded septic patients." 1

Safety Concerns in Infection

  • Intravenous iron should be deferred until soft tissue infections are completely resolved and treated, as it increases circulating non-transferrin-bound iron that promotes pathogen growth. 3
  • A 2021 meta-analysis of 154 RCTs (32,762 participants) demonstrated intravenous iron increases infection risk (RR 1.16,95% CI 1.03-1.29), translating to 16 additional infections per 1,000 patients treated. 1
  • Intravenous iron interferes with "nutritional immunity"—the body's natural process of withholding free iron during infections to limit bacterial growth. 1
  • Common nosocomial pathogens like Staphylococcus aureus and S. epidermidis have iron acquisition mechanisms, and exogenous iron can convert benign colonization into virulent infection. 3

Evidence in Acute Coronary Syndrome

Observational Data Only

  • One observational study of 836 ACS patients found that 29.1% had iron deficiency at baseline, with higher prevalence in women (42.8%) and anemic patients (42.5%). 2
  • Iron deficiency strongly predicted the combined endpoint of non-fatal MI and cardiovascular mortality (HR 1.52,95% CI 1.03-2.26, p=0.037) after adjusting for traditional risk factors. 2
  • This association remained significant (HR 1.73,95% CI 1.07-2.81, p=0.026) even after adjusting for NT-proBNP, troponin, and hemoglobin levels. 2

No Therapeutic Trials

  • No randomized controlled trials have evaluated intravenous iron therapy as an intervention in acute coronary syndrome patients. 2
  • The existing evidence only establishes iron deficiency as a prognostic marker, not whether treating it improves outcomes in ACS.

Relevant Trial Evidence in Related Populations

Heart Failure (Not ACS)

  • Six trials in heart failure with iron deficiency (FAIR-HF, CONFIRM-HF, AFFIRM-AHF, IRONMAN, HEART-FID, FAIR-HF2) including 7,175 patients showed intravenous iron reduced recurrent HF hospitalizations and cardiovascular mortality (RR 0.72,95% CI 0.55-0.89 at 12 months). 4
  • A Bayesian meta-analysis of four heart failure trials (n=3,008) demonstrated reduced recurrent HF hospitalizations and cardiovascular mortality (RR 0.73,95% CI 0.48-0.99). 5
  • These findings apply specifically to chronic heart failure with reduced ejection fraction and iron deficiency, not acute coronary syndrome. 4, 5

Critical Care (Non-Septic)

  • A 2022 systematic review of 8 RCTs (1,198 critically ill adults) found intravenous iron increased hemoglobin at 10-30 days (MD 0.52 g/dL, 95% CI 0.23-0.81) but showed no effect on mortality, infection rates, or ICU duration. 6
  • Evidence quality was very low due to high risk of bias, small sample sizes, and wide confidence intervals. 6
  • These trials excluded septic patients, limiting applicability to infected populations. 1, 6

Clinical Implications

For Sepsis

  • Do not administer intravenous iron during active sepsis given the infection risk and lack of efficacy data in this population. 3
  • If symptomatic anemia requires urgent treatment during active infection, consider red blood cell transfusion instead. 3
  • Defer iron supplementation until infection is completely resolved. 3

For Acute Coronary Syndrome

  • Iron deficiency assessment may have prognostic value in ACS patients, but no evidence supports therapeutic intervention with intravenous iron. 2
  • The decision to treat iron deficiency in ACS patients must balance the 16% increased infection risk against uncertain cardiovascular benefits. 1
  • Well-designed randomized trials with standardized infection definitions are needed before recommending intravenous iron in ACS. 1

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

3
Guideline

Administration of Intravenous Iron in Patients with Active Soft Tissue Infection

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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