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Effects of AGI-1067 and Probucol After Percutaneous Coronary Interventions

2003; Lippincott Williams & Wilkins; Volume: 107; Issue: 4 Linguagem: Inglês

10.1161/01.cir.0000047525.58618.3c

1524-4539

Jean‐Claude Tardif, Jean Grégoire, Leonard Schwartz, Lawrence Title, Louise Laramée, François Reeves, Jacques Lespérance, Martial G. Bourassa, Philippe L. L’Allier, Mitchell Glass, Jean Lambert, Marie‐Claude Guertin,

Cardiac, Anesthesia and Surgical Outcomes

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 mm 2 for placebo, 3.69±2.69 mm 2 for probucol, 2.75±1.76 mm 2 for AGI-1067 70 mg, 3.17±2.26 mm 2 for AGI-1067 140 mg, and 3.36±2.12 mm 2 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 mm 3 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.