Cardiovascular Autophagy: Crossroads of Pathology, Pharmacology and Toxicology
Percutaneous coronary interventions (PCI) have surpassed coronary artery bypass grafting as the most common means for treating coronary artery disease, because of materials improvement, the use of stent and pharmacotherapy. However, despite the variety of mechanical techniques such as dilatation, debulking or conventional stent implantation, the incidence of restenosis on short and mid-term follow-up is still representing an important limitation to PCI. Restenosis is mainly due to elastic recoil, negative vessel remodelling and neointimal proliferation, as a response to vessel injury induced by angioplasty devices. The use of conventional stents has provided an efficient method to avoid elastic recoil and negative vessel remodelling, thus partially reducing restenosis as compared to conventional balloon dilatation. However, neointimal proliferation (biological vessel response to injury caused by stent implantation) is not affected by stenting technique. Thus, the extensive use of coronary stent, even in complex lesions, have produced again a "new" disease: the in-stent restenosis especially in some patients' subset (diabetics) or in some lesion subset (bifurcations, long lesions, small vessels, total occlusions, diffuse disease). Therefore, the main target of today's interventional cardiologists is to resolve this problem. The combination between mechanical control of elastic recoil and negative remodelling (stent) and the control of neointimal proliferation - biological response to vessel injury - (antiproliferative drugs) is the emerging approach against restenosis. This emerging approach consists in using the stent as drug carrier to the target site. Local delivery of antiproliferative or immunosuppressive agents using a drug-coated stent is supposed to inhibit in stent restenosis. The first antiproliferative agents being used successfully in clinical trials are sirolimus and paclitaxel and, so far, the data available of these trials demonstrated a marked reduction of restenosis using sirolimus- and paclitaxel-coated stents as compared to conventional stents. However, many questions are still to be answered and several other clinical trials with drug-eluting stents are ongoing, evaluating safety and efficacy of sirolimus and paclitaxel in a larger number of patients and in different subset of coronary lesions type and morphology. Based on the very impressive results available at the present time, we can expect, in the very near future, remarkable changes in our clinical practice and the beginning of a new "era" of interventional cardiology.