During evolution from percutaneous balloon angioplasty to bare-metal stents (BMS) and, subsequently, drug-eluting stents (DES), early and late (1-year) adverse clinical events have progressively declined . Although novel metal alloy composition, reduced strut thickness, enhanced platform flexibility/conformability and improved polymer biocompatibility and/or resorption have contributed to improved outcomes, beyond 1-year, even “best in class” metallic DES are associated with a 2 % to 3 % annualized rate of device-related events (target lesion failure [TLF]: composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization), which is similar to rates observed following BMS and first-generation DES . The pathogenesis of this ongoing annual hazard, which extends to 15 years or more, involves the presence of a metallic prosthesis that mechanically distorts and constrains the vessel, limiting coronary vasomotion and positive adaptive remodeling while serving as a persistent nidus for chronic inflammation, neoatherosclerosis, and strut fracture with subsequent thrombosis and/or restenosis.