Prévention des resténoses intrastent: vers un traitement in situ In-stent restenosis: towards a local approach?

Résumé

La pose de stents est devenue la principale technique d’angioplastie coronaire percutanée en France, comme dans les autres pays occidentaux. La principale limite de cette technique est la survenue de resténoses au site d’implantation du stent. Les techniques médicamenteuses de prévention, inefficaces dans l’ensemble, souffrent autant d’une méconnaissance de la physiopathologie des resténoses intrastent que d’une inadéquation entre des traitements systémiques et un phénomène biologique éminemment focal. Des traitement locaux prenant en compte ces données physiopathologiques sont donc en cours d’évaluation chez l’homme. Les premiers résultats cliniques des stents imprégnés actifs, qui permettent de délivrer localement de fortes concentrations de substances antiproliférantes (sirolimus, paclitaxel…), sont très prometteurs et suggèrent que ces nouveaux stents devraient probablement révolutionner la pratique de la cardiologie interventionnelle. Quant à la thérapie génique, son application au problème des resténoses nécessite une simplification et une amélioration de l’efficacité des techniques de transfert génique.

Summary

The use of intracoronary stents represent a major breakthrough in the armamentarium of interventional cardiology. Stents reduce significantly the incidence of recurrent stenosis (in-stent restenosis) via an improved post-procedure luminal diameter and an abrogation of the constrictive remodeling of the arterial wall. However, stent-related arterial injury results in intense proliferative and inflammatory responses and severe intimal hyperplasia, which, in 20% to 40% of the patients, may end up with clinically significant in-stent restenosis. Efficient prevention of in-stent restenosis has yet to be found. Systemic treatments have failed because they don’t take into account the specific physiopathology and, most importantly, the focal nature of in-stent intimal hyerplasia. Hence, local prevention appears to be a straightforward approach to the unsolved issue of in-stent restenosis. In situ β- or γ-irradiation (brachytherapy) has received much attention as a curative treatment of in-stent restenosis but is not indicated for prevention. In contrast, drug-releasing stents have been tested in experimental models and have already provided very promising results in randomized clinical trials. Most of clinical studies have been performed with the antiproliferative agents sirolimus and paclitaxel, but other agents are under scrutiny. In addition, important research is carried out, in which the efficacy of antiproliferative genes is investigated. Clearly, drug-releasing stents are on the verge of profoundly modifying our practice of interventional cardiology. However, several questions remain unanswered as regard to the long term efficacy/toxicity and the cost-effectiveness of this new approach.