Published online before print January 6, 2003, doi: 10.1161/01.CIR.0000047525.58618.3C
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(Circulation. 2003;107:552.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Effects of AGI-1067 and Probucol After Percutaneous Coronary Interventions
From the Montreal Heart Institute (J.C.T., J.G., J. Lespérance, M.G.B., P.L.L., J. Lambert, M.-C.G.), Montreal, Canada; Toronto General Hospital (L.S.), Toronto, Canada; Queen Elizabeth II Hospital (L.T.), Halifax, Canada; Ottawa Heart Institute (L.L.), Ottawa, Canada; Notre-Dame Hospital (F.R.), Montreal, Canada; and AtheroGenics (M.G.), Alpharetta, Ga.
Correspondence to Dr Tardif, Montreal Heart Institute, 5000 Belanger St, Montreal, H1T 1C8, Canada. E-mail tardifjc{at}icm.umontreal.ca
Background— AGI-1067, a metabolically stable modification of probucol, is an equipotent antioxidant to probucol but is pharmacologically distinct. In a multicenter trial, we studied whether AGI-1067 reduces restenosis assessed by intravascular ultrasound (IVUS) after percutaneous coronary intervention (PCI) compared with placebo and probucol used as a positive control.
Methods and Results— Two weeks before PCI, 305 patients were randomly assigned to 1 of 5 treatment groups: placebo, probucol 500 mg BID, or AGI-1067 70, 140, or 280 mg once daily. Patients were treated for 2 weeks before and 4 weeks after PCI. Baseline and 6-month follow-up IVUS were interpreted by a blinded core laboratory. Stents were used in 85% of patients. Luminal area at the PCI site at follow-up was 2.66±1.58 mm2 for placebo, 3.69±2.69 mm2 for probucol, 2.75±1.76 mm2 for AGI-1067 70 mg, 3.17±2.26 mm2 for AGI-1067 140 mg, and 3.36±2.12 mm2 for AGI-1067 280 mg (P=0.02 for the dose-response relationship; P
0.05 for AGI-1067 280 mg and probucol versus placebo). There was a mean narrowing of 5.3 mm3 of reference segment lumen in the placebo group and an enlargement in the AGI-1067 140- and 280-mg groups at follow-up (P=0.05 for 140 mg). An increase in QTc interval >60 ms occurred in 4.8% of placebo patients, 17.4% of probucol patients, and 4.8%, 2.4%, and 2.5% of patients in the AGI-1067 groups (P=0.02).
Conclusions— AGI-1067 and probucol reduce restenosis after PCI. In contrast to probucol, AGI-1067 did not cause prolongation of the QTc interval and improved lumen dimensions of reference segments, suggestive of a direct effect on atherosclerosis.
Key Words: antioxidants • coronary disease • atherosclerosis • restenosis
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