Preclinical evaluation of anti-restenotic therapies and drug-eluting stents : efficacy and safety considerations

Abstract

Restenosis is the main drawback of percutaneous coronary interventions (PCI). Recently, drug-eluting stents (DES) were introduced successfully in clinical practice leading to a drop in the post-angioplasty restenosis rate. Nevertheless, safety and efficacy concerns related to the active compounds of such stents still exist. This thesis aimed at the development of a local delivery system, in combination with the cuff-induced mouse model of neointima formation, in order to closely mimic the DES mode-of-action and to further answer to such remaining questions related to this novel technology. Altogether, these comprehensive studies on efficacy and safety of anti-restenotic compounds using a novel developed mouse model of neointimal hyperplasia have resulted in a thorough understanding of the mode-of-action of these anti-restenotic drugs on neointimal hyperplasia inhibition as well as to further assess the potential adverse effects on vessel wall biology and on the (treated) pre-existing underlying atherosclerotic lesions. Especially the discovery of novel anti-restenotic strategies to be used in combination with the DES technology is of specially importance for further preclinical studies in more advance animal models of restenosis (e.g. porcine coronary artery model) as well as directly in the field of interventional cardiology per se.