Effects of AGI-1067 and probucol after percutaneous coronary interventions.
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.


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< or =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.
Tardif
Jean-Claude
JC
Montreal Heart Institute, Montreal, Canada. tardifjc@icm.umontreal.ca
Grégoire
Jean
J
Schwartz
Leonard
L
Title
Lawrence
L
Laramée
Louise
L
Reeves
François
F
Lespérance
Jacques
J
Bourassa
Martial G
MG
L'Allier
Philippe L
PL
Glass
Mitchell
M
Lambert
Jean
J
Guertin
Marie-Claude
MC
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000517:prevention & control; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000517:prevention & control / Q000628:therapy; D023903:Coronary Restenosis / Q000209:etiology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011341:Probucol / Q000031:analogs & derivatives / Q000627:therapeutic use*; D015607:Stents / Q000009:adverse effects; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional; D014654:Vascular Patency / Q000187:drug effects
D000924:Anticholesteremic Agents; D000975:Antioxidants; C471047:succinobucol; D011341:Probucol