Precision stent-free coronary intervention: mechanical suitability, vascular healing, and the current limits of multi-omics

Stent-free and stent-sparing percutaneous coronary intervention (PCI) is increasingly used to avoid permanent metallic implants in selected coronary lesions, most commonly through drug-coated balloon (DCB) angioplasty. Success depends not only on device choice but also on whether the treated segment remains mechanically stable without a scaffold and on how the vessel heals after intervention. This narrative review examines the vascular biology, procedural requirements, clinical evidence, and emerging multi-omics findings relevant to stent-free PCI. Current treatment selection is based mainly on clinical indication, lesion morphology, lesion preparation, residual stenosis, recoil, dissection, final flow, and selective use of intravascular imaging or physiology. Endothelial recovery, thrombo-inflammatory activation, smooth muscle cell plasticity, extracellular-matrix remodeling, and plaque phenotype may further influence later restenosis, dissection healing, and lumen remodeling. Genomic, single-cell, spatial, proteomic, and metabolomic studies provide mechanistic insight into this biological heterogeneity, but most evidence is derived from atherosclerotic tissue, restenosis cohorts, circulating biomarkers, or experimental vascular injury rather than prospectively characterized DCB-treated coronary lesions. No molecular signature has yet been validated to select DCB instead of drug-eluting stents. Stent-free PCI therefore remains a selective clinical and procedural strategy, while future prospective studies must determine whether molecular profiling adds reproducible information beyond established anatomical, imaging, physiological, and procedural variables.