Mechanism of in-stent restenosis after second-generation drug-eluting stents (DES): is it different from bare-metal stents and first-generation DES?

First-generation drug-eluting stents (DES) have dramatically reduced the rate of in-stent restenosis (ISR) and subsequent target lesion revascularization (TLR) compared with bare-metal stents (BMS) (1). However, widespread use of first-generation DES has drawn attention to several unresolved, clinically relevant issues such as late stent thrombosis (ST) and late restenosis (2). Histopathological studies of first-generation DES have revealed that a chronic reaction to components of the permanent polymer reaction may lead to the delayed arterial healing, which is associated with increased risks of late DES failure (3,4). In addition, neoatherosclerosis is suggested as another cause of very late ST and late TLR (5). To overcome these limitations, biocompatible and biodegradable polymers have been developed and equipped with second-generation DES. Recent clinical trials demonstrated that second-generation DES has the improved efficacy and safety compared with those of first-generation DES (6,7). Nevertheless, second-generation DES, as well as first-generation DES, are not immune to ISR. In fact, Cassese et al. reported a large cohort of patients with angiographic surveillance that ISR rate of second-generation DES remains higher than 10% (8). Therefore, it is important to elucidate the mechanism of ISR after second-generation DES compared with that of BMS and first-generation DES, which may play a crucial role in the newly developed DES.