sirolimus and tranilast

Percutaneous coronary intervention (PCI) with stent implantation has revolutionized the treatment of obstructive coronary artery disease. However, the main limitation of this therapy is stent failure, which is usually caused by in-stent restenosis.. The aim of this article is to critically review the literature on the prevention of in-stent restenosis focusing on drug compounds that have reached clinical testing.. The pathophysiological response following PCI includes many possible targets for antirestenosis treatment. Most notable success is seen with sirolimus (and its analogs) and paclitaxel, both of which target vascular smooth muscular cell proliferation. In view of the systemic side effects of both drugs, the high efficacy of local drug delivery methods reduced enthusiasm for systemic therapy. Cilastazol has shown benefit in restenosis reduction particularly in patients at high risk for stent failure, though further study in broader populations is warranted. Probucol showed variable results, but local drug delivery in combination with sirolimus seems promising. A hypothesized independent antirestenotic effect of pioglitazone in patients with diabetes has not been clearly demonstrated. Initial encouraging results with tranilast have not been replicated in a recent large-scale randomized trial. Colchicine and prednisone have shown promising results but require further investigation in larger clinical trials.

Topics: Anti-Bacterial Agents; Antioxidants; Cilostazol; Coronary Restenosis; Drug Delivery Systems; Drug-Eluting Stents; Humans; ortho-Aminobenzoates; Paclitaxel; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Probucol; Sirolimus; Tetrazoles; Tubulin Modulators; Vasodilator Agents

Drug eluting stents have been developed in order to reduce in-stent restenosis observed with a 20 to 40% rate in bare-stents. Neoinitimal smooth muscular cells proliferation have been characterized as the corner stone of in-stent restenosis. Consequently, many anti-mitotic and anti-inflammatory drugs have been evaluated in a new stent generation, so called coated stents or drug eluting stents. Three major components must be considered to evaluate the beneficial effects: the bare-stent, the drug, and the deliverance system, most usually a polymer. For the present, sirolimus eluting stent and paclitaxel eluting stent are available in the market with the european conformity label considering evidence based medicine established in randomized trials. Both stents have been shown to reduce in-stent restenosis incidence to less than 7%. Long-term follow-up still remain expected and would give answers to two safety queries: what is about the incidence of late stent thrombosis, what is about mal-apposition consequences in clinical feature. Utilization of drug eluting stent in clinical practice must considered materials with european conformity and must applied French society of cardiology guidelines restricting implantation to patients who meet high-risk restenosis criteria. Medicoeconomic approach must be considered beneficial at the present only in patients with high restenosis risk. Long-term antiplatelet regimen of aspirin and clopidogrel must be considered to avoid late stent thrombosis.

Topics: Clinical Trials as Topic; Coronary Restenosis; Drug Delivery Systems; Humans; Immunosuppressive Agents; ortho-Aminobenzoates; Paclitaxel; Platelet Aggregation Inhibitors; Sirolimus; Stents; Tacrolimus

Topics: Angioplasty, Balloon, Coronary; Atherectomy, Coronary; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Disease; Coronary Restenosis; Humans; ortho-Aminobenzoates; Paclitaxel; Probucol; Radiotherapy; Sirolimus; Stents; Trapidil

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