In-Stent Restenosis?

Abstract

T he introduction of bare metal stents (BMS) over 30 years ago was a significant milestone in the evolution of percutaneous coronary intervention. Soon after, it was apparent that these stents led to a troubling phenomenon of in-stent restenosis (ISR), which requires repeat revascularization, was associated with increased morbidity and mortality, and posed a therapeutic challenge. The quest for optimal therapy for ISR has begun, but in parallel, continued efforts were devoted to improve the stent technology. These iterations included design and alloy modification, reducing strut thickness, and adding a polymer to elute an antiproliferative drug. Drug-eluting stents (DES) significantly reduced the occurrence of exuberant neointimal proliferation.1 However, in spite of the wide use and experience gained with novel stent technologies and implantation techniques, the rates of ISR in both BMS and DES are still relatively high.2 In a contemporary report on a large cohort (n=10 004), routine angiographic surveillance 6 to 8 months after stent implantation has revealed ISR rates of 30.1%, 14.6%, and 12.2% for BMS, first-generation DES, and second-generation DES, respectively. 3 See Article by Alfonso et alTo optimize the treatment of ISR, it is imperative to identify and understand the major etiologies for ISR that have been traditionally classified and characterized as (1) operator or technique dependent, including stent undersizing, incomplete lesion coverage, stent under expansion, and malapposition; (2) mechanical and design properties of stents that may lead to recoil because of loss of radial force, stent fractures, and altering increase in shear stress; (3) patient-and biologically related conditions, such as metal allergy, local hypersensitivity reactions with immunologic and inflammatory response to the drug or the polymer, often characterized with inflammatory cells and smooth muscle cells that transformed to rigid scar tissue within the stent. This local inflammation can lead to the development of neoatherosclerosis characterized by accumulation of lipid-laden foamy macrophages within the neointima with or without a necrotic core formation and calcification, which can occur years after stent placement. 4 With the introduction of DES, it was apparent that there are differences with respect to the time course and the phenotypic appearance of ISR across the BMS and DES generations, exhibiting a more diffuse and proliferative pattern for BMS versus more focal and soft lesions for the DES, however, more resistant to treatment. 4 Neoatherosclerosis occurs more frequently and at an earlier time in the first-and second-generation DES when compared with BMS.2 These mechanistic complexities make the treatment of ISR even more challenging because both mechanical and biological factors can influence treatment outcomes.Over the years, there were many attempts to find an optimal therapy for ISR; among them there were the high-pressure balloons, scoring balloons, ablative therapy with laser and rotational atherectomy device...

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“…However, metallic stents cause mechanical damage upon implantation and predispose vascular tissue to neointimal hyperplasia and thrombosis. Although less frequent than balloon angioplasty, when neointimal proliferation becomes worse, the artery can be restenosed (in‐stent restenosis) . Therefore, stent technology has evolved to overcome in‐stent restenosis.…”