Stents, paclitaxel-coated

According to ACC/AHA 2007 guidelines, clopidogrel is indicated for up to 12 months in NSTE ACS patients, with a minimum treatment duration of 1 month after placement of a bare-metal stent and 12 months after placement of a sirolimus- or paclitaxel-coated stent. 

An antiproliferative property of paclitaxel has also found another clinical usage in reduction of restenosis. The marketing of paclitaxel-coated stents have been approved in Europe and will be approved in the United States in 2004. An effort has been made to prepare such a conjugate by combing paclitaxel and a nitric oxide donor.C-7 nitroso paclitaxel derivative 120 as its NO donor conjugate exhibited both strong antimmor (20 nM) and antiplatelet (10 pM) activities in vitro, and anti-stenotic activity in the rabbit model, which indicates the beneficial effect of such a conjugation for the treatment of stenotic vessel disease. 

Farb A, Heller PR Shroff S, et al. Pathological analysis of local delivery of paclitaxel via a polymer-coated stent, Circulation 2001 104 473 79. 

Rogers C, Groothuis A, Toegel G, et al. Paclitaxel release from inert polymer material-coated stents curtails coronary in-stent restenosis in pigs [abstr]. Circulation 2000 102(18) ll 1566. 

Hong MK, Komowski R, Bramwell O, et al. Paclitaxel-coated gianturco-roubin II (GR II) stents reduce neointimal hyperplasia in a porcine coronary in-stent restenosis model. Coron Artery Dis 2001 12(6)513-515. 

Lansky AJ, Costa RA, Mintz GS, et al. Non-polymer-based paclitaxel-coated coronary stents for the treatment of patients with de novo coronary lesions angiographic followup of the DELIVER clinical trial. Circulation 2004 109(16) 1948-1954. 

SIBS-coated stents (no paclitaxel) and BMS in the porcine coronary artery model indicate that SIBS has a biologic response comparable with BMS with no adverse impact on vessel biology (Fig, 8),... 

Hong MK, Mintz GS, Lee CW, et al, Paclitaxel coating reduces in-stent intimal hyperplasia in human coronary arteries a serial volumetric intravascular ultrasound analysis from the Asian Paclitaxel-Eluting Stent Clinical Trial (ASPECT). Circulation 2003 107(4/517-520. 

B) chondroitin sulphate and gelatin-coated stent with paclitaxel ... 

Poly(lactide-co-X-caprolactone)-coated stent —Poly(lactide-co- -caprolactone)-coated paclitaxel-releasing stent... 

Although coronary stents have been a breakthrough in the treatment of obstructive coronary disease, there have been adverse effects in patients, such as restenosis. Much research has gone into addressing this situation. Researchers have looked at coating stents for localized drug delivery and results have shown that delivery of a low dose of paclitaxel (PTx shown in Figure 12) has proved to be cytostatic but not cytotoxic [33]. 

Sipos, L., Som, A., Eaust, R., 2005. Controlled deUvery of paclitaxel from stent coatings using poly(hydroxystyrene-b-isobutylene-b-hydroxystyrene) and its acetylated derivative. Biomacromolecules 6 (5), 2570-2582. 

Kelsch, B., Scheller, B., Biedermann, M., et al. Dose response to Paclitaxel-coated balloon catheters in the porcine coronary overstretch and stent implantation model. Invest. Radiol. 46, 255-263 (2011). doi 10.1097/RLI.0b013e31820577df... 

Percutaneous coronary intervention A minimally invasive procedure whereby access to the coronary arteries is obtained through the femoral artery up the aorta to the coronary os. Contrast media is used to visualize the coronary artery stenosis using a coronary angiogram. A guidewire is used to cross the stenosis and a small balloon is inflated and/or stent is deployed to break up atherosclerotic plaque and restore coronary artery blood flow. The stent is left in place to prevent acute closure and restenosis of the coronary artery. Newer stents are coated with antiproliferative drugs, such as paclitaxel and sirolimus, which further reduce the risk of restenosis of the coronary artery. 

PS/PIB/PS block copolymers have been shown to be vascularly compatible. When loaded with paclitaxel and coated on a coronary stent, the composite can deliver the drug directly to arterial walls. 

Heldman AW, Cheng L, Jenkins GM, et al. Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine model of coronary restenosis. Circulation 2001 103( 18) 2289-2295. 

Bloomington, Indiana, U.S.A.) coated with escalating doses of paclitaxel (0,2, 0,7, 1.4, and 2.7 jig/mm2 of stent surface area) applied directly to stent surface. In both trials, there was a dose-dependent effect on the angiographic parameters of restenosis (64). However, clinical outcomes at 6 and 12 months were not improved in these studies (65). The subsequent Drug ELuting coronary stent systems in the treatment of patients with de noVo nativE coronaRy lesions... 

A number of randomized clinical trials (RCTs) have investigated stent-based delivery of paclitaxel. These studies utilized a number of different delivery methods, including polymeric sleeves, nonpolymeric drug delivery and from drug-polymer coatings on stents. 

Taxus (Boston Scientific, Natick, MA, USA) is another FDA-approved stent that is categorized as first generation. In this stent the drug is paclitaxel (1 micro-gram/mm per unit area of stent surface) incorporated in a SIBBS layer coated on a stainless steel stent with 132 micron-thick struts. Only about 5% of the drug is released over the course of the first two months (Figure 3). 

DESs have been the most recent breakthrough in stent technology. DESs consist of a metal stent covered with a thin polymer coating designed to improve vascular compatibility and elute antiproliferative agents. Drugs such as sirolimus (rapamycin) and paclitaxel serve to reduce restenosis by reducing hyperplasia caused by smooth muscle cell proliferation [37, 38]. 

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