Drug-Eluting Stents: the Past, Present, and Future

Abstract

Since the advent of percutaneous coronary intervention, enormous advances have been made in the treatment of coronary artery disease. Angioplasty and bare metal stents were plagued by high rates of restenosis leading to repeat revascularization procedures. Examination of the underlying pathophysiology of restenosis led to the development of drug-eluting stents to reduce neointimal hyperplasia. However, as restenosis rates declined, length of dual antiplatelet therapy use and risk of long-term stent thrombosis associated with drug-eluting stents increased. Subsequent generations have improved each facet of stent design. Novel alloys maintain durability and reduce strut thickness to increase deliverability, biocompatible polymers decrease the inflammatory response and improve drug elution kinetics, and new generations of drugs predictably inhibit restenosis. Developments on the horizon include stents with bioabsorbable polymers and platforms. The purpose of this review is to assess the evolution of stent design and the evidence behind each generation and to peer into the future of stent technology.

Reduction in the Corrosion Rate of Magnesium and Magnesium Alloy Specimens and Implications for Plain Fully Bioresorbable Coronary Artery Stents: A Review

“…On the basis of the lattermost-mentioned characteristic, five broad types are recognized, these being durable, non-drug-eluting (sometimes called "bare metal stents" (BMSs)); durable, polymer-coated, drug-eluting (sometimes, called "drug-eluting stents" (DESs)); partially bioresorbable, drug-eluting (sometimes, simply called "partially bioresorbable stents (PBRSs); fully bioresorbable, non-drug-eluting; and fully bioresorbable, drug-eluting [29] [46]. Within each of these categories, there are sub-types depending on characteristics such as scaffold material (metal or polymer), coating material (polymer or non-polymer), and drug eluted (for example, biolimus, everolimus, paclitaxel, or sirolimus) ( Table 1).…”

“…The choice of modality for a given case is very challenging because it is dictated by a large array of factors, in particular, stage of CAD (for example, stable CAD and acute myocardial infraction), demographic characteristics and health status of the patient (principally, age and comorbidities, such as diabetes mellitus and high risk for bleeding), location of the lesion in the artery (for example, on a curve or immediately followed by a curve or at the left main stem); type of lesion (such as plain single-vessel, bifurcation single-vessel, plain multi-vessel, and calcified lesions); size of the artery (for example, < or >3 mm); degree of occlusion/blockage of the artery (that is, ratio of lesion size to artery size); and presence or absence of ancillary cardiovascular conditions (for example, myocardial infarction, saphenous vein graft disease and diffuse disease requiring 4 ormore stents) [25] [26] [27]. This challenge is manifest in the fact that, in spite of a voluminous body of literature comprising randomized controlled trials (RCTs), systematic review of results of RCTs, and meta-analyses of the results of RCTs in which the subject is either one modality or two or more [21] [28] [29] [30], there is a lack/shortage of evidencebased recommendations. This has led to guidelines; for example, in 2014, the European Society of Cardiology listedpolymer-coated drug-eluting stents and BCA as preferred procedures [30] and European and US guidelines call for the use of a "Heart Team" (comprising clinical cardiologists(s), interventional cardiologist(s), and cardiothoracic surgeon(s)) in making a decision on modality to use for a particular case [15].…”

Development and characterization of an ex vivo arterial long-term proliferation model for restenosis research

“…Endothelial cells of the intima as well as inflammatory cells from subintimal layers release cytokines that induce vascular smooth muscle cells (SMC) to migrate from the media to the intima and proliferate (Salabei and Hill, 2014). Therefore, drug eluting stents (DES) have been developed, which slowly release anti-proliferative substances to the surrounding tissue (Katz et al, 2015). Despite a reduction of the restenosis rate in DES compared with bare metal stents (BMS), late in-stent restenosis (ISR) has not been abolished (Stefanini and Holmes, 2013;Stettler et al, 2007;Akin et al, 2011).…”

Piperine Congeners as Inhibitors of Vascular Smooth Muscle Cell Proliferation

“…Piperine inhibited vascular smooth muscle cell proliferation with an IC 50 of 21.6 µM, as quantified by a resazurin conversion assay. Investigations of ten piperamides isolated from black pepper fruits and 15 synthesized piperine derivatives resulted in the identification of three potent vascular smooth muscle cell proliferation inhibitors: the natural alkaloid pipertipine (4), and the two synthetic derivatives (2E,4E)-N,N-dibutyl-5-(3,5-dimethoxyphenyl)penta-2,4-dienamide (14) and (E)-N,N-dibutyl-3-(naphtho [2,3-d] [1,3]dioxol-5-yl)acrylamide (20). They showed IC 50 values of 3.38, 6.00, and 7.85 µM, respectively.…”

“…In a concentration dependent manner, it revealed an anti-proliferative effect in the resazurin conversion assay, with an IC 50 of 21.6 µM. In order to identify compounds with enhanced activity and to deduce a SAR, nine additional piperamides were isolated from black pepper (2)(3)(4)(5)(6)(7)(8)(9)(10). All ).…”