Iron Chelation Therapy Fails to Prevent Reperfusion Injury After STEMI

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Adjunctive chelation therapy with deferoxamine after the onset of ischemia in patients treated by primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) fails to limit infarct size or improve myocardial salvage. The findings were published online April 11, 2012, ahead of print in Circulation: Cardiovascular Interventions.

Deferoxamine is an extracellular iron chelator that works as an antioxidant and inhibits endothelial cell activation, the paper explains. Based on previous research, the treatment is hoped to improve coronary blood flow.

Researchers led by Stephen J. Duffy, MB, BS, PhD, of the Alfred Hospital (Melbourne, Australia), randomized 60 STEMI patients to receive a 500-mg intravenous bolus dose of deferoxamine immediately before primary PCI followed by a 12-hour infusion (50 mg/kg of body weight; n = 28) or a placebo consisting of normal saline (n = 32). Baseline characteristics were similar for both groups.

No Difference with Iron Chelation

Serum iron levels were decreased with deferoxamine treatment after primary PCI compared with placebo (3.0 ± 2.5 µmol/L vs. 12.6 ± 5.5 µmol/L; P < 0.0001), a difference that persisted until the end of infusion. By 48 hours, serum iron in the treatment group had normalized and was similar to the level seen in the placebo group (10.4 ± 4.6 µmol/L vs. 8.8 ± 2.8 µmol/L; P = 0.24).

The treatment group saw a reduction in plasma F2-isoprostane level, a measure of oxidative stress, compared with the placebo group immediately after primary PCI (2,878 ± 1,461 pmol/L vs. 2,213 ± 579 pmol/L; P = 0.04). Yet plasma C-reactive protein levels indicated similar degrees of inflammation in both groups at admission, after infusion, and 48 hours later.

At 3 days, there were no differences in contrast-enhanced cardiac MRI-determined infarct size (primary endpoint) or myocardial salvage index in the treatment vs. control groups (table 1). Measures of creatine kinase and troponin I also were equivalent.

Table 1. Measures of Reperfusion Injury at 3 Days


(n = 28)

(n = 32)

P Value

Infarct Size

17.4 ± 10.8%

18.6 ± 10.2%


Myocardial Salvage Index

33.8 ± 23.1%

30.8 ± 24.5%


At 3 months, infarct size and myocardial salvage index remained equivalent between the 2 groups. Indices of LV systolic function and volumes and LV mass were also similar between deferoxamine and placebo, though LVEF improved from 49.1 ± 10.1% to 56.0 ± 11.6% in the treatment group (P = 0.01) and from 48.9 ± 5.4% to 52.4 ± 7.2% in the control group (P = 0.01).

The researchers considered deferoxamine treatment to be relatively safe, with 1 death occurring in the treatment group and 2 in the placebo group. Also, the 3-month cumulative incidence of heart failure was similar between the groups (P = 0.70).

Limitations Aplenty

Dr. Duffy and colleagues admit the study may be limited by its small sample size, but they also propose another explanation for the lack of effect: deferoxamine may simply not behave as had been expected.

“Iron-catalyzed [reactive oxygen species] generation may not be a major contributor to ischemia-reperfusion injury in STEMI in humans,” they write. “Previous cardiovascular studies with [deferoxamine] in humans have been exclusively in [the] setting of cardiopulmonary bypass, a potent stimulant of oxidative stress. However, cardiopulmonary bypass is a vastly different clinical scenario to STEMI.”

Lastly, because the drug is “poorly cell permeable and predominantly acts as an extracellular iron chelator, this can potentially limit the success of intracellular iron chelation and the reduction of intracellular [reactive oxygen species] generation and cytotoxicity.”


Chan W, Taylor AJ, Ellims AH, et al. Effect of iron chelation on myocardial infarct size and oxidative stress in ST-elevation myocardial infarction. Circ Cardiovasc Interv. 2012;Epub ahead of print.



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  • Dr. Duffy reports no relevant conflicts of interest.

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