tranilast and succinobucol

Despite significant advances in technology and technique, coronary restenosis remains the primary limitation of percutaneous transluminal coronary angioplasty (PTCA). Among patients undergoing PTCA, between 20% and 50% of patients who do not receive a stent and 10%-30% of those who do receive a stent develop restenosis within 6 months of the procedure. Drug-eluting stents, which release high local concentrations of antiproliferative or immunosuppressive agents directly into the vessel wall at the site of the lesion, have dramatically reduced the incidence of restenosis in patients undergoing PTCA. However, even with drug-eluting stents, a significant percentage of higher-risk patients develop in-stent restenosis. These data suggest that a role remains for effective, well-tolerated systemic pharmacologic therapies to further reduce the rate of restenosis. To date, the majority of systemic agents tested for restenosis prevention have failed to show significant benefit. Only 2 agents, probucol and cilostazol, have consistently demonstrated efficacy in preventing restenosis. In addition, the investigational agent AGI-1067 has demonstrated promising efficacy in early clinical trials. Together with drug-eluting stents, these therapies may for the first time reduce the rate of restenosis to near zero, even in high-risk patients, such as individuals with diabetes mellitus.

Topics: Angioplasty, Balloon, Coronary; Cilostazol; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Drug Therapy, Combination; Humans; ortho-Aminobenzoates; Pioglitazone; Platelet Aggregation Inhibitors; Probucol; Risk Factors; Stents; Tetrazoles; Thiazolidinediones; Trapidil; Treatment Outcome

In this article, the authors intend to provide an update on clinical trials of pharmacologic prevention of restenosis after percutaneous coronary interventions, placed in the perspective of the use of orally administered therapy for the prevention of atherosclerosis progression and clinical events.. AGI-1067, the mono-succinic acid ester of probucol, is a phenolic antioxidant member of a novel class of agents termed v-protectants. It has strong antioxidant properties equipotent to those of probucol and antiinflammatory properties. It inhibits gene expression of VCAM-1 and MCP-1 and has been effective at preventing atherosclerosis in all tested animal models including the non-human primate. In the Canadian Antioxidant Restenosis Trial (CART) 1, AGI-1067 and probucol improved lumen dimensions at the site of percutaneous coronary intervention. AGI-1067 also improved luminal dimensions of non-intervened coronary reference segments in the Canadian Antioxidant Restenosis Trial, which suggests a direct antiatherosclerosis effect. Probucol reduced post-percutaneous coronary intervention restenosis and progression of carotid atherosclerosis in other clinical trials. Although statins reduce atherosclerotic events, they do not appear to have a significant effect on restenosis. The failure of folate therapy to protect against restenosis in the Folate After Coronary Intervention Trial (FACIT) occurred despite significant reductions in homocysteine levels.. Prevention of both post-percutaneous coronary intervention restenosis and atherosclerosis progression with a pharmacologic agent such as AGI-1067 may be an attractive treatment paradigm. Two important trials that test the antioxidant/antiinflammatory hypothesis are ongoing with AGI-1067: the Canadian Atherosclerosis and Restenosis Trial 2, which assesses its value for the reduction of both atherosclerosis progression and post-percutaneous coronary interventions restenosis, and the Aggressive Reduction of Inflammation Stops Events (ARISE) trial which is evaluating its effects on cardiovascular events.

Topics: Anti-Inflammatory Agents; Anticholesteremic Agents; Antioxidants; Clinical Trials as Topic; Coronary Artery Disease; Coronary Restenosis; Folic Acid; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; ortho-Aminobenzoates; Oxidative Stress; Probucol; Sirolimus; Vitamins