In Stent Neo-Atherosclerosis: Pathophysiology, Clinical Implications, Prevention, and Therapeutic Approaches

Abstract

Despite the dramatic improvements of revascularization therapies occurring in the past decades, a relevant percentage of patients treated with percutaneous coronary intervention (PCI) still develops stent failure due to neo-atherosclerosis (NA). This histopathological phenomenon following stent implantation represents the substrate for late in-stent restenosis (ISR) and late stent thrombosis (ST), with a significant impact on patient’s long-term clinical outcomes. This appears even more remarkable in the setting of drug-eluting stent implantation, where the substantial delay in vascular healing because of the released anti-proliferative agents might increase the occurrence of this complication. Since the underlying pathophysiological mechanisms of NA diverge from native atherosclerosis and early ISR, intra-coronary imaging techniques are crucial for its early detection, providing a proper in vivo assessment of both neo-intimal plaque composition and peri-strut structures. Furthermore, different strategies for NA prevention and treatment have been proposed, including tailored pharmacological therapies as well as specific invasive tools. Considering the increasing population undergoing PCI with drug-eluting stents (DES), this review aims to provide an updated overview of the most recent evidence regarding NA, discussing pathophysiology, contemporary intravascular imaging techniques, and well-established and experimental invasive and pharmacological treatment strategies.

Global research trends in in-stent neoatherosclerosis: A CiteSpace-based visual analysis

“…In contrast, the formation of ISNA has become a key factor predisposing to long-term coronary complications, including late ISR (>1 year) and very late stent thrombosis ( 20 ). Despite the use of next-generation drug-eluting stents, late stent failure rate has not been effectively controlled, and ISNA is a factor that cannot be ignored ( 35 ). Therefore, it is extremely necessary to pay attention to the research progress in the field of ISNA, which may provide new methods for ISR prevention and treatment.…”

Glycaemic Control in Patients Undergoing Percutaneous Coronary Intervention: What Is the Role for the Novel Antidiabetic Agents? A Comprehensive Review of Basic Science and Clinical Data

“…Specifically, GLP-1 prevents the progression of atherosclerotic lesions by inhibiting the formation of macrophage foam cell clusters [114]. Concordantly, liraglutide has been reported to prevent the development of atherosclerotic plaques through the suppression of macrophage foam cell formation by down-regulation of acyl-CoA:cholesterol acyltransferase 1 (ACAT1) [115], responsible for cholesterol ester accumulation [116]. Semaglutide, another GLP-1 RA, showed to decrease inflammation and pro-atherogenic mechanisms through the reduction of cytokine levels (i.e., TNF-α and interferon γ [IFN-γ]) and immune cells activation, recruitment, and adhesion [117].…”

The Diagnostic Value of Circulating Biomarkers and Role of Drug-Coated Balloons for In-Stent Restenosis in Patients with Peripheral Arterial Disease

“…However, in-stent restenosis (ISR) after stenting of the FP district remains a daunting problem, resulting in a less than 50% patency rate after 3 years [ 4 ]. ISR is believed to be due to neointimal hyperplasia caused by post-PTA endothelial damage [ 5 , 6 ], but similarly to coronary stent disease, other factors are involved such as adherence to antiplatelet therapy [ 7 , 8 ] and specific stent factors [ 9 ]. The incidence of ISR also varies according to the type of stent used: 19–35% at 1 year with a grooved tube nitinol stent, and 14–17% with a twisted-wire nitinol stent [ 4 ].…”

“…Balloon dilatation and stent implantation is associated with vascular injury, followed by repair processes that include endothelialization and neointimal formation, providing for the activation of the inflammatory response and the release of blood inflammatory markers [ 9 , 10 , 11 ]. The analysis of these biomarkers could prove useful to physicians to predict an eventual predisposition to ISR.…”