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is a place in indonesia where peopel are said to roam around aimlessley and which produce the largest amount of incestous tribes in the world. however, epopel ofver look this problem due to the rising prositution outbreak. | journal = ] | volume = 109 | pages = 701–706 | doi = 10.1161/01.CIR.0000116202.41966.D4
In ], a '''drug-eluting stent''' is a ] (a scaffold) placed into narrowed, diseased ] that slowly releases a ] to block ] proliferation. This prevents scar-tissue–like growth that, together with clots (thrombus), could otherwise block the stented artery.

Heart attacks, or ]s, are major causes of death and disability; they result when a portion of heart muscle dies from inadequate blood flow. This typically occurs at sites where coronary arteries are already narrowed and damaged. Inflammation in the artery wall causes injury; excessive tissue growth and cholesterol deposition occur, and clots form. These narrowings are prone to being suddenly blocked, or a piece may break off and block a smaller branch downstream. If blood flow can be restored early enough, permanent damage can be prevented, and preemptive restoration can prevent heart attacks from occurring in the first place.

Coronary artery stents, typically a metal framework, can be placed inside the artery to help keep it open. However, the stent is a foreign object (not native to the body), and it incites an immune response. This may cause scar tissue (cell proliferation) to rapidly grow over the stent. In addition, there is a strong tendency for clots to form at the site where the stent damages the arterial wall. Since ]s are involved in the clotting process, patients must take ] therapy afterwards, usually ] for six months and ] indefinitely.<ref name="G&G"> {{cite book
| last = Michel | first = Thomas | editor = Laurence L. Brunton, John S. Lazo, & Keith L. Parker
| title = ] | origyear = 1941 | edition = 11th ed. | year = 2006
| publisher = McGraw-Hill | location = New York | pages = 842 | chapter = Treatment of Myocardial Ischemia
}}</ref> However, the antiplatelet therapy may be insufficient to fully prevent clots; these and the cell proliferation may cause the standard (“bare-metal”) stents to become blocked. Drug-eluting stents were designed to lessen this problem; by releasing an antiproliferative drug (drugs typically used against cancer or as ]s), they can help avoid this ''in-stent restenosis'' (re-narrowing).

Drug-eluting stents have been shown to be superior for many of the conditions that traditional stents (“bare-metal stents”) have been used; they have been highly successful at treating coronary heart disease, and offer significant advantages over other therapies, such as surgery. In the few years since their ] approval in 2003, the use of drug-eluting stents has become one of the dominant interventions in preventing and treating ].<ref name="NEJM review">{{cite journal
| last = Serruys | first = Patrick W. | coauthors = Michael J.B. Kutryk, and Andrew T.L. Ong | date = ] | title = Coronary-Artery Stents
| journal = ] | volume = 354 | issue = 5 | pages = 483–495 | url = http://content.nejm.org/cgi/content/extract/354/5/483|id = PMID 16452560
}} (extract)</ref><sup>, </sup><ref name="FDA Cypher">{{cite web
| url = http://www.fda.gov/cdrh/mda/docs/p020026.html| title = New Device Approval — Cypher Sirolimus-eluting Coronary Stent| accessdate = 2006-07-22
| publisher = ]
}}</ref>

==Structure==
Drug-eluting stents consist of three parts. The stent itself is an expandable framework, usually metal. Added to this is a drug to prevent the artery from being re-occluded, or blocked. These typically have been drugs already in use as anti-cancer drugs or drugs that suppress the immune system, although new drugs are being developed specifically for drug-eluting stents. Finally, there must be a carrier which slowly releases the drug over months. The carrier is typically a ], although ] or ceramics are also being researched.<ref name="NEJM review" /> Different carriers release the loaded drug at different rates.

==Placement==
A ] with a guide wire is used to place the stent; it is loaded in its collapsed form onto a balloon at the end of the catheter. The device is then introduced through a ], usually at the groin through one of the ]. It is threaded back towards the ]. In the ] just prior to entering the heart, the appropriate coronary artery is entered. The balloon is inflated, cracking and compressing the ] and expanding the stent. The balloon may be inflated and deflated several times. The balloon and catheter are then withdrawn, leaving the stent in place. The stent releases its drug over the next several months.

==Current devices==
Currently, two models of drug-eluting stents are used. Both drugs currently in use are previously developed drugs used for other purposes; their use to prevent in-stent proliferation is relatively new.

The first successful type releases ] (rapamycin), a powerful immunosuppressive and antiproliferative drug. It is primarily used as an immunosuppressant to prevent organ transplant rejection. Produced by the bacterium ''] hygroscopicus'', binds to the ] FKBP-12. The resulting complex inhibits the ] (mTOR), which has several effects, including preventing the cell from duplicating its genetic material; it blocks the ] at the G<sub>1</sub>&rarr;S transition.<ref name="G&G sirolimus">{{cite book
| last = Krensky | first = Alan M. | coauthors = Flavio Vincenti, & William M. Bennett |editor = Laurence L. Brunton, John S. Lazo, & Keith L. Parker
| title = ] | origyear = 1941 | edition = 11th ed. | year = 2006
| publisher = McGraw-Hill | location = New York | pages = 1413 | chapter = Immunosuppressants, Tolerogens, and Immunostimulants
}}</ref> A sirolimus-eluting stent is produced by ] (]), and marketed under the name ''Cypher''. This stent is made of ] and uses a polymer as the carrier.<ref name="FDA Cypher" />

A second model uses ], another antiproliferative drug; it is primarily used against various forms of cancer. Derived from the ] tree, paclitaxel binds to and stabilizes ]s. Without the dynamic framework provided by these components of the ], the cell cannot undergo ] and so is arrested at the M stage.<ref name="G&G paclitaxel">{{cite book
| last = Chabner| first = Bruce A. | coauthors = Philip C. Amrein, Brian J. Druker, M. Dror Michaelson, Constantine S. Mitsiades, Paul E. Goss, David P. Ryan, Sumant Ramachandra, Paul G. Richardson, Jeffrey G. Supko, & Wyndham H. Wilson |editor = Laurence L. Brunton, John S. Lazo, & Keith L. Parker
| title = ] | origyear = 1941 | edition = 11th ed. | year = 2006
| publisher = McGraw-Hill | location = New York | pages = 1352–1353 | chapter = Antineoplastic Agents
}}</ref> The paclitaxel-eluting stent produced by ] is marketed under the name ''Taxus''. Like the Cypher stent, the Taxus stent is made of stainless steel and uses a polymer as drug carrier.<ref name="FDA Taxus">{{cite web
| url = http://www.fda.gov/cdrh/mda/docs/p030025.html| title = New Device Approval — P030025 — TAXUS™ Express<sup>2</sup>™ Paclitaxel-Eluting Coronary Stent System
| accessdate = 2006-07-22| date = ]| publisher = ]
}}</ref>

==History==
]
The first procedural method to treat blocked coronary arteries was a type of open-heart surgery called ] (CABG) surgery, which uses a section of vein or artery from elsewhere in the body to bypass the diseased vessel. In 1977, ] introduced ] (PTCA), in which a catheter was introduced through a peripheral artery and a balloon expanded to compress and crack the obstructive plaque.<ref name="NEJM Gruntzig">{{cite journal
| last = Grüntzig | first = AR | authorlink = Andreas Grüntzig | coauthors = A Senning, & WE Siegenthaler
| date = ] | title = Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty
| journal = ] | volume = 301 | issue = 2 | pages = 61–68
| url = http://content.nejm.org/cgi/content/abstract/301/2/61 | accessdate = 2006-07-22 | id = PMID 449946
}} (abstract)</ref>

As equipment and techniques improved, the use of PTCA rapidly increased, and by the mid-1980s, PTCA and CABG were being performed at equivalent rates.<ref name="Harrison's"> {{cite book
| last = Baim | first = Donald S. | editor = Dennis L. Kasper, Anthony S. Fauci, Dan L. Longo, Eugene Braunwald, Stephen L. Hauser, & J. Larry Jameson
| title = ] | origyear = 1958 | edition = 16th ed. | year = 2005 | publisher = McGraw-Hill
| location = New York | pages = 1459–1462 | chapter = Percutaneous Coronary Revascularization
}}</ref>. PTCA could only be used on limited scenarios, and the vessels had a high rate (30–40% in six months) of ]; additionally, 3% required emergency bypass surgery.<ref name="Harrison's" />. Dotter and Judkins had suggested using intraluminal prosthetic devices to maintain blood flow (in arteries of the leg) in 1964,<ref name="Dotter">{{cite journal
| last = Dotter | first = Charles T. | coauthors = & Melvin P. Judkins | year = 1964 | title = Transluminal Treatment of Arteriosclerotic Obstruction
| journal = ] | volume = 30 | pages = 654–670 | url = http://circ.ahajournals.org/cgi/content/abstract/30/5/654
| accessdate = 2006-07-22 | id = PMID 14226164
}} (abstract)</ref> and in 1986, Puel and Sigwart implanted the first stent in humans.<ref name="NEJM review" /> Several trials in the 1990s showed the superiority of stent placement to simple balloon angioplasty, and stent placement became increasingly prevalent, reaching 84% of percutaneous interventions by 1999.<ref name="NEJM review" />

Initial difficulties included blood clotting and occluding the stent in the hours or days after placement.<ref name="Harrison's" /> Coating the stent with biologically inert substances like platinum or gold did not help.<ref name="NEJM review" /> Eventually, using high balloon pressures to tightly fix the stent against the vessel and anticoagulation with aspirin and (usually) clopidogrel were established; these eliminated most of the difficulty with in-stent thrombosis.<ref name="NEJM review" /><sup>, </sup><ref name="Harrison's" />

Difficulties still remained, however, with the formation of scar tissue inside the stent (in-stent neointimal hyperplasia) and clotting problems not addressed by the antiplatelet drug regimen. The stent itself was a logical choice for delivering medication. The slow release of drugs from the stent spares the patient the inconvenience of taking yet another medication, and prevents the danger of the patient forgetting to take or losing interest in taking the medicine. But more importantly, a stent that releases a drug can deliver high concentrations directly to the target region, analagous to placing a medicated cream on a skin problem or taking an inhaler to help the lungs or airways. Taking the medication orally or intravenously would require much higher doses as it was distributed throughout the body to ensure that a sufficient concentration would be reached at the target; this could cause unacceptable side effects or patient injury.

The first successful trials were of sirolimus-eluting stents. A successful trial in 2002 led to approval of the Cypher stent in Europe, followed by FDA approval in the U.S. in 2003.<ref name="NEJM review" /> Soon thereafter, a series of trials of paclitaxel-eluting stents led to FDA approval of the Taxus stent in 2004.<ref name="FDA Taxus" />

==Uses==
There has been considerable research showing the benefits of coronary stents. Data specifically on drug-eluting stents are less abundant, though where studied, they have usually been shown to be superior to bare-metal stents, and in some cases, may be used for lesions for which surgery was previously the only option. Drug-eluting stents are used both for restoring blood flow immediately after a heart attack and also electively for improving blood flow in a compromised vessel. Only certain types of blockages are amenable to stent placement, though drug-eluting stents may be successful in lesions for which bare-metal stents were insufficient. Drug-eluting stents are used to reopen grafts from prior CABG surgery that have themselves become blocked, and also can be used for in-stent restenosis in prior stents.<ref name="NEJM review" />

==Current research==
Research focuses on establishing the roles for drug-eluting stents and for developing new types of stents. Different materials for all three components—the scaffolding, the carrier, and the drug—are being actively investigated.

In place of the stainless steel 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 ] alloy–based stent has been tested in animals, though there is currently no carrier for drug elution.<ref name="Heart magnesium">{{cite journal
| last = Heublein | first = B. | coauthors = R. Rhode, V. Kaese, N. Niemeyer, W. Hartung, & A. Haverich | year = 2003
| title = Biocorrosion of magnesium alloys: a new principle in cardiovascular implant technology? | journal = ]
| volume = 89 | pages = 651–656 | url = http://heart.bmjjournals.com/cgi/content/full/89/6/651 | accessdate = 2006-07-23| id = PMID 12748224
}}</ref> 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; ]<ref name="Tsjui">{{cite journal
| last = Tsuji | first = T. | coauthors = H. Tamai, K. Igaki, E. Kyo, K. Kosuga, T. Hata, T. Nakamura, S. Fujita, S. Takeda, S. Motohara, & H. Uehata
| year = 2003 | title = Biodegradable stents as a platform to drug loading. | journal = International Journal of Cardiovascular Interventions
| volume = 5 | issue = 1 | pages = 13–6 | id = PMID 12623560
| accessdate = 2006-07-22
}}</ref> and ]<ref name="Vogt">{{cite journal
| last = Vogt
| first = Felix
| coauthors = Andreas Steina, Gösta Rettemeier, Nicole Krott, Rainer Hoffmann, Jürgen vom Dahl, Anja-Katrin Bosserhoff, Walter Michaeli, Peter Hanrath, Christian Weber, & Rüdiger Blindt | year = 2004 | title = Long-term assessment of a novel biodegradable paclitaxel-eluting coronary polylactide stent
| journal = European Heart Journal | volume = 25 | pages = 1330–1340 | url = http://eurheartj.oxfordjournals.org/cgi/content/full/25/15/1330 | accessdate = 2006-07-22 | id = PMID 15288161
}}</ref> have been used as eluted drugs.

There are also several other anti-proliferative drugs under investigationin human clinical trials. In general, these are analogues of sirolimus. Like sirolimus, these block the action of mTOR. ] has developed ]; unlike sirolimus and paclitaxel, this sirolimus analogue designed for use in stents with ] as a carrier. Their ZoMaxx stent is a zotarolimus-eluting, stainless steel and ]–based stent; a modified ] slowly releases the zotarolimus.<ref name="Abbott ZoMaxx">{{cite web
| url = http://www.abbott.com/global/url/content/en_US/30.20.50:50/general_content/General_Content_00024.htm
| title = Vascular Devices| accessdate = 2006-07-23| publisher = ]}}</ref> Zotarolimus has been licensed to ] who is researching the effectiveness in a drug-eluting stent of their own. Their Endeavor stent also uses phosphorylcholine to carry the zotarolimus; the stent is a ] alloy.<ref name="NEJM review" /> The Endeavor stent was approved for use in Europe in 2005.

Clinical trials are currently examining two stents carrying ],<ref name="NEJM review" /> an immunosuppressant that like sirolimus is used to prevent organ rejection.<ref name="G&G sirolimus" /> ], which has the exclusive license to use everolimus in drug-eluting stents, is the manufacturer of both stents. The Champion stent uses a bioabsorbable polylactic acid carrier on a stainless steel stent.<ref name="FUTURE">{{cite journal
| last = Grube | first = Eberhard | coauthors = Shinjo Sonoda, Fumiaki Ikeno, Yasuhiro Honda, Saibal Kar, Charles Chan, Ulrich Gerckens, Alexandra J. Lansky, & Peter J. Fitzgerald | year = 2004 | title = Six- and Twelve-Month Results From First Human Experience Using Everolimus-Eluting Stents With Bioabsorbable Polymer
| journal = ] | volume = 109 | issue = | pages = 2168—2171 | doi = 10.1161/01.CIR.0000128850.84227.FD | id = PMID 15123533
}}</ref><sup>, </sup><ref name="Guidant Champion">{{cite web
| url = http://www.guidant.com/news/400/web_release/nr_000459.shtml| title = Guidant News Release — April 5, 2004| accessdate = 2007-07-23| date = ]
| publisher = ]
}}</ref> In contrast, its Xience stent uses a durable (non-bioabsorbale) polymer on a cobalt stent.<ref name="Guidant Xience">{{cite web
| url = http://www.guidant.com/news/500/web_release/nr_000551.shtml| title = Guidant News Release — June 22, 2005| accessdate = 2006-07-23
| date = ]| publisher = ]
}}</ref>

==Complications and controversy==
In the last several years, drug-eluting stent use has become exceedingly popular, both in place of surgery and for lesions not severe enough for surgery. Placing stents is not without risk, however, and the recent development of the drug-eluting stents means that long-term data, especially in comparison to traditional bare-metal stents, are not available. As enthusiasm for the new devices abates, there is some concern about overzealous use of stents in general.

As with all cardiac catheterization, there are several risks. Patients may exhibit severe allergic response to the contrast agents used to visualize the coronary arteries, and occasionally, the peripheral entry artery fails to properly heal after the catheter is removed, causing a collection of blood called a ]. Rarely, a coronary artery can be perforated while the catheter is advanced or during stent placement.<ref name="Harrison's" />

Finally, stent occlusion can occur. Thrombosis may occur during the procedure, in the following days, or much later. Stents cause damage to the vessel wall, and, as foreign objects, they provoke inflammation and clot formation. And tissue proliferation in the stent can cause the vessel to narrow again. Patients with stents (but not those undergoing isolated balloon angioplasty) must remain on an antiplatelet drug like clopidogrel for at least three to six months; discontinuing it, even for a short time, can cause a clot to form;<ref name="Harrison's" /> aspiring must be taken for life.<ref name="NEJM review" /> Drug-eluting stents have been shown to have significantly lower rates of in-stent proliferation compared to bare-metal stents. However, some studies suggest that the proliferation may be merely delayed; when the drug has been completely eluted, proliferation may occur.<ref name="NEJM review" /> The magnitude and significance of this effect is unclear. Rarely, a type of allergic reaction to the drug may occur; episodes of fatality have been reported.<ref name="hypersensitivity">{{cite journal
| last = Virmani | first = Renu | coauthors = Giulio Guagliumi, Andrew Farb, Giuseppe Musumeci, Niccolo Grieco, Teresio Motta, Laurian Mihalcsik, Maurizio Tespili, Orazio Valsecchi, & Frank D. Kolodgie | year = 2004 | title = Localized Hypersensitivity and Late Coronary Thrombosis Secondary to a Sirolimus-Eluting Stent
| journal = ] | volume = 109 | pages = 701–706 | doi = 10.1161/01.CIR.0000116202.41966.D4
| id = PMID 14744976 | id = PMID 14744976
}}</ref> }}</ref>

Revision as of 14:41, 26 July 2006

An example of a drug-eluting stent. This is the TAXUS™ Express™ Paclitaxel-Eluting Coronary Stent System, which releases paclitaxel.

is a place in indonesia where peopel are said to roam around aimlessley and which produce the largest amount of incestous tribes in the world. however, epopel ofver look this problem due to the rising prositution outbreak. | journal = Circulation | volume = 109 | pages = 701–706 | doi = 10.1161/01.CIR.0000116202.41966.D4 

| id = PMID 14744976

}}</ref>

Nevertheless, coronary stents, and drug-eluting stents in particular, have revolutionized the treatment of coronary heart disease, and new techniques and materials that may ameliorate these problems are being studied. Bioabsorble or biodegradable polymer or stent may help avoid the inflammation and other side effects of long-term foreign objects. Different carriers affect the rate of release of drug, and different antiproliferative drugs may have different clinical effects. The success of drug-eluting stents in coronary disease has prompted investigation of their use in other narrowed arteries, such as the carotid arteries leading to the brain. Such use remains investigational.

References

  1. Cite error: The named reference NEJM review was invoked but never defined (see the help page).
  2. Boulos, A. S. (2005). "Preliminary evidence supporting the safety of drug-eluting stents in neurovascular disease". Neurological Research. 27 Suppl 1: S95–102. PMID 16197833. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

Further reading

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