In vivo cardiovascular assays for drug discovery: evolution of the drug-eluting stent.
Percutaneous intervention using balloon angioplasty accompanied by stent implantation has become the predominant procedure to treat occlusive coronary and peripheral vascular disease. Unfortunately, restenosis associated with intimal hyperplasia and arterial remodeling at the stented site occurs within 6 months in 20 to 30% of cases. To address this problem, the concept of utilizing a stent as the vehicle to deliver agents locally and limit the overexuberant tissue response related to its placement has been developed. Targeting excess arterial wall smooth muscle cell proliferation, preclinical studies have demonstrated the efficacy of two drugs, paclitaxel and rapamycin, in both in vitro and in vivo animal studies. Early, as well as large, randomized clinical studies using polymer-coated, drug-eluting stents have clearly demonstrated a significant and dramatic efficacy in reducing restenosis rates and improving clinical outcomes compared with the use of the bare stent for revascularization procedures. Despite the low incidence of late thrombosis associated with the rapamycin- and paclitaxel-eluting stents, some concerns remain (such as the need for sustained anticoagulant therapy), providing the impetus for developing coated stents that promote rather than inhibit endothelial healing in order to limit the restenotic response.
Sprague
Eugene A
EA
Department of Radiology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. sprague@uthscsa.edu
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D023903:Coronary Restenosis / Q000150:complications / Q000517:prevention & control; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008954:Models, Biological; D016032:Randomized Controlled Trials as Topic; D015607:Stents
D002317:Cardiovascular Agents