Understanding and managing in-stent restenosis: a review of clinical data, from pathogenesis to treatment

Abstract

The lumen diameter reduction after percutaneous coronary intervention (PCI) is well known as "restenosis". This phenomenon is due to vessel remodeling/recoil in case of no-stent strategy or, in case of stent employ, "neointimal proliferation" that consists in an excessive tissue proliferation in the luminal surface of the stent otherwise by a further new-occurring atherosclerotic process called "neoatherosclerosis". The exact incidence of in-stent restenosis (ISR) is not easy to determine caused by different clinical, angiographic and operative factors. In the pre-stent era the occurrence of restenosis ranged between 32-55% of all angioplasties, and drop to successively 17-41% in the bare metal stents (BMS) era. The advent of drug-eluting stent (DES), especially 2nd generation, and drug-coated balloon (DCB) further reduce restenosis rate until <10%. We here review the main characteristics of this common complication of coronary interventions, from its pathogenesis to the most appropriate treatment strategy.

Keywords: In-stent restenosis (ISR); bare metal stents (BMS); drug-coated balloon (DCB); drug-eluting stent (DES); paclitaxel-eluting balloon (PEB); stent thrombosis (ST).

Figure 1

Focal ISR according to angiographic classification of Mehran et al. (46). (A) ISR type IA: articulation or gap (black arrow is the ISR between the proximal and distal edges in white arrows); (B) ISR type IB: margin (black arrow is the ISR in correspondence of distal edge of stent between white arrows); (C) ISR type IC: focal body (black arrow is the ISR between the proximal and distal edges in white arrows); (D) ISR type ID: multifocal (black arrows highlight ISR at proximal and distal edge). ISR, in-stent restenosis.

Figure 2

Diffuse ISR according to angiographic classification of Mehran et al. (46). (A) ISR type II: intra-stent (black arrows highlight the restenosis involving all the stent length); (B) ISR type III: proliferative (black arrow highlights the restenosis involving proximal and distal vessel tracts over stent length); (C) ISR type IV: total occlusion (black arrow highlights the total occlusion of coronary artery at the proximal stent edge). ISR, in-stent restenosis.

Figure 3

Histology view of drug-eluting stent ISR of porcine coronary arteries [(A) red arrow indicates neoatherosclerosis above stent struts, stent struts perimeter delimited by white dots highlighted by white arrow], from Takimura et al. (51). IVUS images of drug-eluting stent ISR [(B) red arrow indicates neoatherosclerosis above stent struts, stent perimeter indicate by white arrow]. OCT images of drug-eluting stent ISR (C) with cross-sectional (upper) and longitudinal (down) views (stent struts perimeter is highlighted by white arrows; red arrow indicates neoatherosclerosis above stent struts). OCT analysis have a high tissue resolution looks like histology one. ISR, in-stent restenosis; IVUS, intra-vascular-ultrasound; OCT, optical-coherence-tomography.