• Héctor M García-García, Sophia Vaina, Keiichi Tsuchida, and Patrick W Serruys.
• Department of Interventional Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands.
• Arch Cardiol Mex. 2006 Jul 1; 76 (3): 297-319.

AbstractStent implantation was developed to overcome the acute recoil and high restenosis rate of balloon angioplasty, but resulted in the development of chronic in-stent restenosis related to specific factors regarding patient, stent, lesion and procedural characteristics. Some factors are not modifiable, such as patient and lesion characteristics, whereas procedural characteristics may be improved by better implantation technique and stent design. Drug-eluting stents are a novel approach in stent technology and design with local drug delivery to inhibit intimal thickening by interfering with different pathways involved in the development of inflammation, migration, proliferation and/or secretion of the extracellular matrix. Both the drug and the delivery vehicle must fulfill pharmacological, pharmacokinetic and mechanical requirements. Current successful drug eluting stents require a polymer coating for drug delivery. Clinical trials examining several pharmaceutical agents, particularly sirolimus and paclitaxel, have demonstrated marked reduction in restenosis following stenting. Sirolimus is a natural macrocyclic lactone and paclitaxel is a cytotoxic agent against many tumors. Both compounds block cell cycle progression and thus inhibit smooth muscle cell proliferation. The development of drug-eluting stents is one of the major revolutions in the field of Interventional Cardiology. Restenosis rate has been significantly reduced, in comparison to bare metal stents. The ideal drug to prevent restenosis must have an anti-proliferative and anti-migratory effect on smooth muscle cells but on the other hand must also enhance re-endothelialization, in order to prevent late thrombosis. Additionally, it should effectively inhibit the anti-inflammatory response after balloon induced arterial injury. Currently sirolimus, paclitaxel and more recently, ABT-578-eluting stents are commercially available, but ongoing research and clinical trials will result in new stents coming to market with novel designs loaded with a variety of compounds. As drug-eluting stent implantation becomes more liberal leading to an extensive use of this technology, the problem of restenosis in drug-eluting stents will become more common. However, for the time being, little is known regarding optimal treatment of in-stent restenosis following drug-eluting stent implantation. Future research is mandatory to further clarify, whether these patients should be treated with the same drug-eluting stent, with a different drug-eluting stent or with increased doses. Further improvements, including expansion of drug-loading capacity, coatings with programmable pharmacokinetic capacity and the discovery of new drugs may in the future further enhance the efficacy and safety of these stents. Although, drug-eluting stents have significantly reduced angiographic restenosis rate and have improved the clinical outcome, late thrombosis and restenosis remain an important subject of ongoing research. As drug-eluting stents are extensively used to treat all lesions, more efficacious agents and improved stent platforms are required. Synthetic or biological polymers can be used as matrixes for drug incorporation, but concerns have been raised regarding biocompatibility, sterility or potential induction of inflammation. Currently, alterations on stent-backbone design (biodegradable, bioabsorbable, nanoporous etc.) are being explored. Clearly, the anti-proliferative compounds sirolimus and paclitaxel have dominated up to date clinical practice, whereas their analogues are readily emerging. In the future, however, it is likely that drugs, currently under investigation, will address additional mechanisms associated with neointimal formation leading to restenosis, either as single agents or in combination with anti-proliferative compounds.

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