Drug-Eluting Stents

Abstract

The introduction of percutaneous transluminal coronary angioplasty has revolutionized the field of cardiology by providing patients with coronary artery disease immediate and effective therapy. Overshadowing the early success of angioplasty was the high rate of angiographic restenosis and recurrent symptoms at 6 months. The use of stents reduced the incidence of restenosis; however, the rise in the number of patients undergoing percutaneous interventions produced a new problem of restenosis occurring within the stent: in-stent restenosis (ISR). Mechanical approaches, including directional and rotational atherectomy and systemic pharmacotherapy, have failed to demonstrate a reduction in ISR in randomized clinical trials. Intravascular brachytherapy is currently the only approved therapy for ISR, although this treatment has numerous unresolved questions and is not effective in a large percent of patients. Drug-eluting stents have reduced the incidence of restenosis by providing localized therapy to the targeted lesion without systemic toxicity. The purpose of this review is to synthesize data from major clinical trials involving the 2 most successful agents used in the prevention of restenosis: sirolimus and paclitaxel. The cellular and molecular mechanisms of both ISR and restenosis postangioplasty derived from animal models will be introduced. Second, an overview of 3 alternate interventions that attempt to reduce the rates of restenosis is presented. Finally, the major randomized, controlled trials involving sirolimus and paclitaxel are described, and their clinical implications and use as a possible solution in the prevention of restenosis is discussed.

Vessel Ultrasound Sonographic Assessment of Soluble Receptor for Advanced Glycation End Products Efficacy in a Rat Balloon Injury Model

“…These remodeling processes are intensified especially in patients with diabetes. Although effective in combating neointima hyperplasia, current anti-inflammatory and antimitotic drugs often display significant side effects and toxicity that deem systemic applications unfeasible, and their local delivery is achieved via drug-eluting stents [7], [8]. Therapeutic reagents that can be administered systemically stand the benefit of providing alternative avenues for treating acute vascular injuries as well as circumventing overall chronic inflammation in the vasculature 9 …”

Use of a novel anti-proliferative compound coated on a biopolymer to mitigate platelet-derived growth factor-induced proliferation in human aortic smooth muscle cells: comparison with sirolimus

“…The act of introducing a stent in a vessel results in injury to the vascular wall causing endothelial denudation and inflammation subsequently leading to a regenerative response in the vascular smooth muscle cells involving their proliferation, migration and accumulation of extracellular matrix in response to growth factors like PDGF and inflammatory cytokines like tumor necrosis factor (TNF-α) [16][17][18][19]. A DES has three main components: metal stent backbone, a non-biodegradable polymer coating and the drug contained in the coating.…”

“…This is achieved by coating conventional stents with a polymer coating loaded with an immunosuppressant or an antiproliferative drug which ensures their delivery in an effective dose to the site of injury and inflammation, thus reducing neointimal hyperplasia without reaching toxic levels in the blood [16,20]. The biochemical nature of the polymer and its interaction with the living tissues inside the blood vessel is vital for limiting the amount of local inflammation [16]. The commonly used DES has a non-biodegradable coating that remains in the body after the drug elutes completely [16].…”

“…The biochemical nature of the polymer and its interaction with the living tissues inside the blood vessel is vital for limiting the amount of local inflammation [16]. The commonly used DES has a non-biodegradable coating that remains in the body after the drug elutes completely [16]. This may lead to complications such as exaggerated inflammatory response, local toxicity, polymer breakdown and erosion, and incompatibility with humoral factors [16,21,22].…”

“…The commonly used DES has a non-biodegradable coating that remains in the body after the drug elutes completely [16]. This may lead to complications such as exaggerated inflammatory response, local toxicity, polymer breakdown and erosion, and incompatibility with humoral factors [16,21,22]. It is therefore desirable to use biocompatible, biodegradable inert, non-thrombogenic polymer coatings on the stents that can tolerate mechanical stress [23,24].…”