Neoatherosclerosis From a Pathologist's Point of View.

Abstract

Percutaneous coronary interventions using drug-eluting stents (DES) or bare metal stents (BMS) are the most commonly performed procedures for the management of acute coronary syndromes and stable angina.1 BMS, introduced >2 decades ago, were limited by complications of in-stent restenosis (ISR) with the need for repeat revascularization in up to one third of patients.2 DES with controlled release of antiproliferative agents developed in the past decade were specifically designed to inhibit neointimal formation and reduce restenosis within the stented coronary segment and have achieved greater success, particularly with the development of newer platforms aimed at improving the safety and efficacy. The commonly used antiproliferative drugs are highly lipophilic molecules that exert immunosuppressive effects in the case of sirolimus group of drugs by inhibiting the mammalian target of rapamycin, which prevents the degradation of p27kip1, a cyclin-dependent kinase inhibitor that plays an important role in regulating vascular smooth muscle cell (VSMC) migration and proliferation,3 whereas paclitaxel is a cytotoxic drug known to suppress VSMC and endothelial cell proliferation and migration by disrupting microtubule dynamics, thus affecting cells in the mitotic phase of the cell cycle.4 The first generation of DES (namely Cypher [Cordis Corp, Miami Lakes, FL] and Taxus [Boston Scientific, Natick, MA]) had unique disadvantages of thick metallic struts, and uneven and thick coatings of poorly biocompatible permanent polymers were used to load drugs. However, despite therapeutic efficacy and recommendations to extend dual antiplatelet therapy for at least 12 months, complications of late stent thrombosis (LST, >1 month to ≤1 year) and very late stent thrombosis (VLST, >1 year) have emerged as a significant limitation, particularly with approved first-generation DES.5 More recently, however, complications of in-stent neoatherosclerosis with associated plaque rupture have seemed to be a major contributing factor for late DES failure and as …