Vascular protectants for the treatment of atherosclerosis.
AGI-1067, the monosuccinic acid ester of probucol, is a phenolic antioxidant member of a novel class of agents termed vascular protectants. It has strong antioxidant properties, equipotent to those of probucol, and anti-inflammatory properties. It inhibits gene expression of vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 and has been effective at preventing atherosclerosis in all tested animal models. It also improved luminal dimensions of reference segments in the percutaneous coronary intervention (PCI) vessels in the CART-1 clinical trial, which suggests a direct anti-atherosclerosis effect. Two important trials that test the antioxidant/anti-inflammatory hypothesis are ongoing with AGI-1067: the Canadian Atherosclerosis and Restenosis Trial, which assesses its value for the reduction of both atherosclerosis progression in non-PCI vessels and post-PCI restenosis, and the Aggressive Reduction of Inflammation Stops Events trial, which is evaluating the effects of AGI-1067 on hard cardiovascular outcomes.
Tardif
Jean-Claude
JC
Montreal Heart Institute, 5000 Belanger Street, Montreal, PQ, H1T 1C8, Canada. tardifjc@icm.umontreal.ca
Grégoire
Jean
J
Lavoie
Marc-André
MA
L'Allier
Philippe L
PL
D000975:Antioxidants / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000517:prevention & control*; D006801:Humans; D011341:Probucol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D020011:Protective Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012107:Research Design
D000975:Antioxidants; D020011:Protective Agents; C471047:succinobucol; D011341:Probucol