The BMJ August 19, 2026

Intravenous iron to treat anaemia before cardiac surgery (ITACS): international, double blind, placebo controlled randomised trial

Paul S Myles, Andrew A Klein, Julian A Smith, et al.

Bottom Line

In anemic adults undergoing elective cardiac surgery, preoperative intravenous iron significantly reduced the need for red cell transfusion and resulted in a modest but statistically significant increase of one extra day alive and at home in the 90 days after surgery compared to placebo.

Key Findings

1. The median number of days alive and at home up to 90 days after surgery was 81.1 days (IQR 74.8-83.7) in the intravenous iron group compared with 80.0 days (IQR 69.5-83.6) in the placebo group (adjusted median difference 1.0 day, 95.4% CI 0.0 to 2.1 days, P=0.041).

2. Red cell transfusions were administered to 61.1% (262 patients) in the IV iron group versus 68.2% (302 patients) in the placebo group during their hospital stay (relative risk 0.89, 95% CI 0.81 to 0.98).

3. Intravenous iron administration saved approximately 44 units of blood products for every 100 patients treated.

4. There were no significant differences in the rates of major complications or length of hospital stay between the two groups.

Study Design

Design

RCT

Double-Blind

Sample

955

Patients

Duration

90 days

Median

Setting

33 hospitals, 10 countries

Population Adults (aged 18 years or older) with anemia (hemoglobin concentration <130 g/L), with or without known iron deficiency, scheduled to undergo elective on-pump or off-pump cardiac surgery.

Intervention Intravenous iron (1,000 mg of ferric carboxymaltose or similar product) administered 1 to 26 weeks prior to the planned surgery.

Comparator Matched placebo administered 1 to 26 weeks prior to the planned surgery.

Outcome Number of days alive and at home up to 90 days after surgery.

Study Limitations

• The absolute improvement of 1 day alive and at home over a 90-day recovery period is a very small clinical treatment effect size.

• Enrollment required the presence of anemia but did not mandate confirmation of absolute iron deficiency, potentially diluting the effect in patients whose anemia was driven by other non-iron etiologies.

• The highly variable timing of the intervention (1 to 26 weeks prior to surgery) may have led to inconsistent erythropoietic responses by the time of the surgical date.

Clinical Significance

ITACS provides high-quality evidence that administering intravenous iron 1 to 26 weeks before elective cardiac surgery is an effective and safe component of perioperative patient blood management. While its impact on overall recovery days and major complications is marginal, it meaningfully reduces reliance on allogeneic red blood cell transfusions, saving critical blood bank resources without safety trade-offs.

Historical Context

Preoperative anemia affects up to one-third of patients awaiting cardiac surgery and is a known independent predictor of increased morbidity, mortality, and red cell transfusion requirements. Prior to this study, systematic reviews (such as a 2024 meta-analysis) and smaller trials established that preoperative IV iron could reduce transfusion rates (from roughly 53% to 40%), but they lacked sufficient power to demonstrate clear improvements in patient-centered outcomes. The ITACS trial was designed as the definitive large-scale international study to ascertain whether optimizing hemoglobin with IV iron could meaningfully improve 'days alive and at home', a validated, multidimensional and patient-centric measure of post-surgical recovery.

Guided Discussion

High-yield insights from every perspective

Med Student

Medical Student

Why is intravenous iron preferred over oral iron in the immediate preoperative period for patients undergoing elective cardiac surgery?

Key Response

Oral iron requires weeks to months to adequately replenish stores and raise hemoglobin, and its absorption is often blunted by hepcidin in inflammatory states. IV iron bypasses the gut, allowing for rapid replenishment of iron stores and more robust erythropoiesis in the short preoperative window before surgery.

Resident

How should the finding of a one-day increase in 'days alive and at home' over a 90-day period influence your shared decision-making with a patient who is hesitant to undergo an additional preoperative infusion visit?

Key Response

While statistically significant, a one-day difference may not be clinically meaningful to every patient, especially if the IV infusion requires taking a day off work or traveling. Residents must weigh the primary benefit of reduced transfusion risk against the logistical burden, framing the outcome as a marker of a smoother recovery rather than a dramatic survival benefit.

Fellow

The ITACS trial administered IV iron to all anemic patients regardless of their baseline iron panel. How does this 'blanket' approach to preoperative anemia compare pathophysiologically and practically to targeted therapy based on ferritin and TSAT levels?

Key Response

Cardiac surgery patients often have functional iron deficiency due to chronic inflammation where ferritin is normal or high but TSAT is low. A blanket approach simplifies preoperative logistics by avoiding wait times for lab results, but it risks giving iron to patients with non-iron deficient anemias, highlighting the tension between protocolized Patient Blood Management and precision medicine.

Attending

Given the logistical challenges of scheduling preoperative IV iron infusions for elective cardiac surgeries, how can healthcare systems restructure their preoperative pathways to implement the ITACS findings without delaying time-sensitive surgeries?

Key Response

Attendings must consider systems-based practice. Implementing this requires early identification of anemia at the time of surgical referral rather than the pre-admission testing clinic a week before surgery. Establishing automated reflex testing and dedicated preoperative anemia clinics can optimize hemoglobin without delaying operative intervention.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD

The ITACS trial used 'days alive and at home at 90 days' as a continuous composite outcome. What are the statistical and interpretative advantages and limitations of using this metric compared to traditional time-to-event or dichotomous composite outcomes in perioperative trials?

Key Response

Days Alive and Out of Hospital is a patient-centered, continuous composite that integrates mortality, length of stay, and readmissions, increasing statistical power. However, it can be heavily skewed since most patients have high values, complicating parametric analyses, and it assumes a day in the hospital is equally bad regardless of the cause, which can mask specific mechanistic benefits or harms.

Journal Editor

When reviewing a trial that demonstrates a minimal but statistically significant difference in a composite outcome like 1 extra day alive and at home out of 90, what specific methodological checks would you perform to ensure this result is not driven by ascertainment bias, loss to follow-up, or competing risks?

Key Response

A reviewer would scrutinize missing data handling methods such as multiple imputation and the distribution of the outcome metric. Since a 1-day difference is tiny in a 90-day window, even slight differential loss to follow-up or differences in discharge practices between study sites could artificially drive the statistical significance, threatening internal validity.

Guideline Committee

Current Patient Blood Management guidelines strongly recommend identifying and treating preoperative anemia but often leave the exact threshold and modality to clinical discretion. Based on ITACS, should guidelines mandate preoperative IV iron for all anemic cardiac surgery patients, and what level of evidence would this represent?

Key Response

ITACS provides high-quality Level 1 evidence that IV iron reduces transfusions. However, a guideline committee would likely issue a conditional recommendation for universal IV iron due to the modest clinical benefit of 1 extra day at home and existing cost and logistical barriers. They would weigh this against existing Society of Thoracic Surgeons guidelines, potentially updating them to specifically favor IV over oral iron in tight preoperative windows.

Clinical Landscape

Noteworthy Related Trials

2015

TITRe2 Trial

n = 2,003 · NEJM

Tested

Restrictive transfusion threshold (hemoglobin < 7.5 g/dL)

Population

Patients with postoperative anemia after cardiac surgery

Comparator

Liberal transfusion threshold (hemoglobin < 9.0 g/dL)

Endpoint

Infection or ischemic events within 3 months

Key result: There was no significant difference in the composite of infection or ischemic events, though mortality was unexpectedly higher in the restrictive group at 90 days.

2017

TRICS III Trial

n = 5,243 · NEJM

Tested

Restrictive red-cell transfusion threshold (hemoglobin < 7.5 g/dL)

Population

Patients with moderate-to-high risk undergoing cardiac surgery

Comparator

Liberal transfusion threshold (hemoglobin < 9.5 g/dL)

Endpoint

Composite of death, myocardial infarction, stroke, or new-onset renal failure with dialysis

Key result: A restrictive transfusion strategy was non-inferior to a liberal strategy regarding major adverse clinical outcomes.

2020

PREVENTT Trial

n = 487 · Lancet

Tested

Intravenous ferric carboxymaltose

Population

Anemic patients undergoing major open abdominal surgery

Comparator

Placebo

Endpoint

Death or blood transfusion within 30 days

Key result: Preoperative intravenous iron did not reduce the need for blood transfusion or death compared to placebo in patients undergoing major abdominal surgery.

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