Canadian Antioxidant Restenosis Trial - CART


The goal of this study was to assess the efficacy of AGI-1067, a metabolically stable modification of the antioxidant probucol, in reducing restenosis following PCI


AGI-1067 reduces restenosis as assessed by IVUS after PCI compared with placebo and probucol.

Study Design

Study Design:

Patients Enrolled: 305
Mean Follow Up: 5-7 months

Patient Populations:

Scheduled to undergo PCI with or without stenting on >=1 native coronary artery and had >=1 de novo target lesion with luminal narrowing >=50%.


Severe liver disease or serum creatinine >=200 mmol/L; MI in prior 7 days; left main stenosis >50%; ejection fraction <30%; PCI for another lesion in the preceding 6 months; were being treated for a restenotic lesion; had scheduled atherectomy, brachytherapy, or PCI of bypass graft; required therapy with a class Ia/III antiarrhythmic agent; or had significant QTc lengthening before randomization.

Primary Endpoints:

Minimal lumen area on IVUS 6 months after PCI

Drug/Procedures Used:

Patients were randomly assigned to AGI-1067 70, 140, or 280 mg once daily, probucol 500 mg twice daily, or placebo beginning 14 days before scheduled PCI and continuing for 4 weeks following PCI. All patients also received an extra dose of AGI-1067 280 mg or probucol 1000 mg or matched placebos on the evening before PCI, according to random treatment assignment.

Concomitant Medications:

Aspirin 325 mg/d was given for duration of study. PCI with or without stent placement and post-PCI management were performed according to current clinical practice. All patients treated with stents also received clopidogrel 75 mg/d for 30 days after PCI.

Principal Findings:

Stents were implanted in 85.1% of patients. Luminal area immediately following PCI was improved in a dose-response fashion in the AGI-1067 arms (p=0.04). Luminal area at the PCI site on 6-month IVUS was 2.66 mm2 for placebo, 3.69 mm2 for probucol, 2.75 mm2 for AGI-1067 70 mg, 3.17 mm2 for 140 mg, and 3.36 mm2 for 280 mg (p=0.02 for dose-response; p=0.046 for AGI-1067 280 mg and p=0.01 for probucol vs placebo). The reference segment lumen narrowed in the placebo arm (-5.3 mm3) but enlarged in the 140 mg AGI-1067 arm (3.5 mm3, p=0.05 vs placebo) and trended to be larger in the 280 mg arm (p=0.09). There was only minimal change in the probucol arm (-0.2 mm3, p=NS). There were no differences by treatment arm in the clinical outcomes of death, MI, or target lesion revascularization. The QTc interval increased >60 ms at least once during the study in 4.8% of patients in the placebo arm, 17.4% of patients in the probucol arm, and 4.8%, 2.4%, and 2.5% of patients in the AGI-1067 70, 140, and 280 mg arms, respectively (p=0.02).


Treatment with the antioxidant AGI-1067 or probucol was associated with a larger luminal area at the PCI site on 6 month IVUS. Additionally, reference segment lumen diameter was larger on follow-up in the higher dose AGI-1067 arms but did not differ from placebo in the probucol arm. Of concern was the significantly higher rate of QTc prolongation in the probucol arm compared with placebo. The CART-2 trial is currently evaluating the use of a longer duration of treatment with AGI-1067 on neointimal formation and restenosis and clinical outcomes.


Circulation. 2003;107:552-558.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease

Keywords: Coronary Artery Disease, Probucol, Stents

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