Immune-Mediated Coronary Stent Failure: From PCI-Induced Vascular Injury to In-Stent Restenosis, Neoatherosclerosis and Stent Thrombosis

Percutaneous coronary intervention (PCI) treats focal coronary obstruction by compressing plaque, injuring the vessel wall, and placing a metallic or bioresorbable scaffold. Most treated segments heal, but a small minority enter a prolonged, excessive, or unstable repair state that contributes to in-stent restenosis (ISR), in-stent neoatherosclerosis, and stent thrombosis (ST). Human evidence is strongest for delayed healing, uncovered struts, macrophage-rich neoatherosclerosis, and hypersensitivity-associated late thrombosis, whereas routine immune biomarker-guided care remains unsupported. The practical question addressed here is therefore not whether inflammation participates, which is established, but which immune signals, read together with intravascular imaging, could realistically change post-PCI management. The narrowed lumen is only the visible endpoint; beneath it sits vascular repair shaped by device-material exposure, local haemodynamics, and host immunity. Endothelial denudation and platelet activation initiate fibrin deposition, complement signalling, and release of damage-associated molecular patterns (DAMPs). Neutrophils, monocytes, and macrophages dominate early, followed by lymphocytes and vascular smooth muscle cells that remodel the repair compartment. Drug-eluting stents (DES) have markedly reduced early neointimal hyperplasia, yet selected late failures still involve delayed endothelial recovery, chronic peristrut inflammation, hypersensitivity, and neoatherosclerotic transformation. Immune biology is useful at the bedside only when interpreted with procedural context, device design, and patient phenotype. Imaging-defined endpoints and paired immune phenotyping are therefore needed to guide treatment by mechanism instead of angiography or isolated biomarkers.