What are the results of the Ironman (Intensive Randomized Trial to Evaluate Implantable Cardioverter-Defibrillators) trial?

From the Guidelines

The Ironman trial is not mentioned in the provided evidence, and therefore, its results cannot be determined from the given information. However, the evidence provided discusses the benefits and cost-effectiveness of implantable cardioverter-defibrillators (ICDs) in various patient populations, including those with heart failure and reduced ejection fraction.

Key Findings

• The evidence suggests that ICDs can reduce mortality and improve outcomes in certain patient populations, such as those with previous myocardial infarction, left ventricular ejection fraction (LVEF) ≤35%, and nonsustained ventricular tachycardia (VT) 1.
• The MADIT-II trial showed that patients with previous MI and LVEF <30% had a mortality benefit with ICDs, regardless of heart failure class 1.
• The SCD-HEFT trial demonstrated that patients with ischemic and nonischemic cardiomyopathy, LVEF ≤35%, and heart failure class II to III had a benefit with an ICD compared to amiodarone or placebo 1.
• The economic outcomes of ICD implantation for primary prevention of sudden cardiac death (SCD) were assessed in several studies, which reported increased survival and life expectancy, but also higher lifetime costs of medical care with an ICD 1.

Clinical Implications

• The evidence supports the use of ICDs in patients with heart failure and reduced ejection fraction, particularly those with a history of myocardial infarction or nonsustained VT.
• The decision to implant an ICD should be based on individual patient characteristics, including LVEF, heart failure class, and the presence of ventricular arrhythmias.
• The economic value of ICDs should be considered in the context of the patient's overall clinical profile and the potential benefits of improved survival and reduced sudden cardiac death.

Limitations

• The evidence provided does not mention the Ironman trial, and therefore, its results cannot be determined.
• The studies discussed in the evidence have varying patient populations and inclusion criteria, which may limit the generalizability of the findings to other patient groups.

From the Research

Results of the Ironman Trial

The Ironman trial, also known as the Intravenous Iron or Placebo for Anaemia in Intensive Care trial, was a randomized, placebo-controlled, blinded trial that aimed to test the hypothesis that early administration of intravenous iron, compared with placebo, reduces allogeneic red blood cell transfusion during hospital stay and increases the haemoglobin level at the time of hospital discharge 2. The trial results showed that:

• The iron group received 97 red blood cell units versus 136 red blood cell units in the placebo group, yielding an incidence rate ratio of 0.71 [95 % confidence interval (0.43-1.18), P = 0.19] 2.
• Median haemoglobin at hospital discharge was significantly higher in the intravenous iron group than in the placebo group [107 (interquartile ratio IQR 97-115) vs. 100 g/L (IQR 89-111), P = 0.02] 2.
• There was no significant difference between the groups in any safety outcome 2.

Subsequent Analyses of the Ironman Trial

Subsequent analyses of the Ironman trial data have been conducted to investigate the effect of correcting iron deficiency on the risk of serious infection in heart failure:

• The results suggested that correcting iron deficiency is not associated with an increased risk of hospitalization or death from infection, and may reduce such events, especially when TSAT is <20% 3.
• The composite primary event of interest tended to be lower in those randomized to FDI when analysed as first (hazard ratio [HR] 0.79,95% confidence interval [CI] 0.62-1.01, p = 0.055) or recurrent event (rate ratio 0.85,95% CI 0.64-1.13, p = 0.089) 3.
• Further analyses suggested that the reduction in hospitalizations due to infection with FDI was restricted to patients with TSAT <20% 3.

Relationship Between Iron Deficiency and Clinical Response

The relationship between blood tests for iron deficiency, including anaemia, and the response to intravenous iron in patients with heart failure has also been investigated:

• The rise in haemoglobin after administering FDI, adjusted for usual care, was greater for lower baseline TSAT (Pinteraction < .0001) and ferritin (Pinteraction = .028) and more severe anaemia (Pinteraction = .014) 4.
• MLwHF scores at 4 months were somewhat lower (better) with FDI for more anaemic patients (overall Pinteraction = .14; physical Pinteraction = .085; emotional Pinteraction = .043) but were not related to baseline TSAT or ferritin 4.
• The absence of anaemia or a TSAT ≥ 20% was associated with lower event rates and little evidence of benefit from FDI 4.

Key findings of the Ironman trial include:

• Intravenous iron did not result in a significant lowering of red blood cell transfusion requirement during hospital stay 2.
• Patients who received intravenous iron had a significantly higher haemoglobin concentration at hospital discharge 2.
• Correcting iron deficiency is not associated with an increased risk of hospitalization or death from infection, and may reduce such events, especially when TSAT is <20% 3.