In-stent Restenosis (ISR)

In-stent restenosis (ISR) remains a major problem after percutaneous coronary intervention (PCI), defined as >50% narrowing of the lumen of a stented artery, generally accompanying angina or proven by fractional flow reserve (FFR < 0.80) or intravascular ultrasonography (IVUS).

The main cause of ISR is neointimal hyperplasia after artery injury caused by balloon angioplasty or placement of a stent. The roles of platelet activation, thrombus development, and inflammatory responses are involved in ISR. Activated neutrophils and macrophages release cytokines and growth factors, which induce the up-regulation of genes such as c-myc and increase the proliferation and migration of SMC. Metalloproteinases remodel the extracellular matrix, depositing excess material that narrows the lumen 3–6 months after PCI.

The risks of in-stent restenosis (ISR) range from 16% to 44% for bare-metal stents (BMS) and from 3% to 20% for drug-eluting stents (DES), influenced by factors such as diabetes, lesion length, small artery diameter, and procedural variables like stent underexpansion or geographic miss. Focal (restricted to stent segments) or widespread patterns are guides to prognosis.

Management stresses best-first deployment and second-generation DES for recurring ISR. Therapeutic options include drug-coated balloons (DCB), extra DES, or brachytherapy with IVUS-guided preparation to improve results. The yearly ISR incidence remains 1-2%, emphasising the continued necessity for revascularisation.