A drug-eluting stent (DES) is a coronary stent (a scaffold) placed into narrowed, diseased coronary arteries that slowly releases a drug to block cell proliferation. This prevents fibrosis that, together with clots (thrombus), could otherwise block the stented artery, a process called restenosis. The stent is usually placed within the coronary artery by an Interventional cardiologist during an angioplasty procedure.
Drug-eluting stents in current clinical use were approved by the FDA after clinical trials showed they were statistically superior to bare-metal stents (BMS) for the treatment of native coronary artery narrowings, having lower rates of major adverse cardiac events (MACE) (usually defined as a composite clinical endpoint of death + myocardial infarction + repeat intervention because of restenosis
Drug-eluting stents consist of three parts. Stent platform, coating, and drug.
The stent itself is an expandable metal alloy framework. Many DES are based on a bare-metal stent (BMS). The stents have elaborate mesh-like designs to allow expansion, flexibility and in some cases the ability to make/enlarge side openings for side vessels. Cobalt chrome alloy is stronger (and more radio-opaque) than the usual 316L stainless steel so the struts can be thinner which seems to reduce the degree of restenosis. (The L605 CoCr alloy has less nickel than 316L stainless steel and so may cause less allergy.)
A coating, typically of a polymer, holds and elutes (releases) the drug into the arterial wall by contact transfer. The first few DES licenced used durable coatings, but some newer coating are designed to biodegrade after or as the drug is eluted. Coatings are typically spray coated or dip coated. There can be one to three or more layers in the coating eg a base layer for adhesion, a main layer for holding the drug, and sometimes a top coat to slow down the release of the drug and extend its effect.
The drug is mainly to inhibit neointimal growth (due to proliferation of smooth muscle cells) which would cause restenosis. Much of the neointimal hyperphasia seems to be cause by inflammation. Hence immunosuppressive and antiproliferative drugs are used. Both sirolimus and paclitaxel were previously used for other medical applications; new drugs are being evaluated for coronary stents [7] [28].
Examples (approved for clinical use) :
Cypher (J&J, Cordis ) uses a 316L stainless steel BxVelocity stent (140 µm struts) and adds a 12.6 µm 3 layer coating (2 µm Parylene C base coat, 10 µm main coat of PEVA, PBMA and sirolimus, and a 0.6 µm top coat of PBMA).[29] The sirolimus elutes over a period of about 30 days [30].
Taxus (Boston Scientific) uses a 316L stainless steel Express2 stent (132 µm struts) and adds a 16 µm single layer Translute SIBS copolymer coating containing paclitaxel which elutes over a period of about 90 days [30].
Endeavour (Medtronic) uses a cobalt chrome Driver stent (91 µm struts) and adds a 4.3 µm phosphorylcholine coating that includes zotarolimus, on a 1 µm base coat.
Xience V (Guidant, Abbott) uses an L605 cobalt chrome ML Vision stent (81 µm struts) and adds a 7.6 µm fluropolymer multilayer coating with drug everolimus [31].
Examples approved outside the US :
Infinnium (Sahajanand Medical Technologies) Matrix Stent Platform, contains biodegradable polymers as a drug delivery vehicle with Paclitaxel [32]
Axxion (Biosensors Int) Stainless steel stent, Synthetic Glycocalix coating with paclitaxel[33].
BioMatrix (Biosensors Int) S stent platform, bioabsorbable PLA coating with Biolimus A9 drug [34].
ARTAX (Aachen Resonance) double helix stainless steel platform, without polymer, metal coated with paclitaxel drug [35].
[edit] Investigation and Alternative drugs
There are also several other anti-proliferative drugs under investigation in human clinical trials. In general, these are analogues of sirolimus. Like sirolimus, these block the action of mTOR. Medtronic has developed zotarolimus; unlike sirolimus and paclitaxel, this sirolimus analogue designed for use in stents with phosphorylcholine as a carrier. Their ZoMaxx stent is a zotarolimus-eluting, stainless steel and tantalum–based stent; a modified phosphorylcholine slowly releases the zotarolimus [36]. Zotarolimus has been licensed to Medtronic which is researching the effectiveness in a drug-eluting stent of their own. Their Endeavor stent, which is a cobalt alloy,[7] also uses phosphorylcholine to carry the zotarolimus was approved for use in Europe in 2005 is now close to U.S. FDA approval [37].
Clinical trials are currently examining two stents carrying everolimus,[7] an analog of sirolimus. Guidant, which has the exclusive license to use everolimus in drug-eluting stents, is the manufacturer of both stents. The Guidant vascular business was subsequently sold to Abbott [38]. The Champion stent uses a bioabsorbable polylactic acid carrier on a stainless steel stent [39] [40]. In contrast, its Xience stent uses a durable (non-bioabsorbable) polymer on a cobalt alloy stent [41].
One alternative to drug-eluting stents is a stent surface designed to reduce the neointimal proliferation. One such is the Genous bioengineered stent [42].
In place of the stainless steel (and now cobalt chrome) currently used in stents, various biodegradable frameworks are under early phases of investigation. Since metal, as a foreign substance, provokes inflammation, scarring, and thrombosis (clotting), it is hoped that biodegradable or bioabsorbable stents may prevent some of these effects. A magnesium alloy–based stent has been tested in animals, though there is currently no carrier for drug elution. [43] A promising biodegradable framework is made from poly-L-lactide, a polymer of a derivative of L-lactic acid. One of these stents, the Igaki-Tamai stent, has been studied in pigs; tranilast [44] and paclitaxel[45] have been used as eluted drugs
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