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In medicine, a drug-eluting stent is a stent (a metal scaffold) placed into diseased coronary arteries that slowly releases a drug blocking cell proliferation; this helps to delay or prevent the artery from being re-occluded by smooth muscle and clot (thrombus). The stent consists of a expandable metal framework, a drug to prevent restenosis, and a carrier to slowly release the drug. It is placed over a balloon on a catheter and guide wire and introduced through a peripheral artery, usually one of the femoral arteries. It is threaded back towards the heart; from the aorta, the appropriate coronary artery is entered. The balloon is inflated, cracking and compressing the plaque and expanding the stent. The balloon and catheter are then withdrawn, leaving the stent in place. The stent releases its drug over the next several months. Patients must take antiplatelet therapy afterwards, usually clopidogrel for six months and aspirin indefinitely. Drug-eluting stents have been shown to be superior for many of the conditions that traditional stents (“bare-metal stents”) have been used, and have become quite popular since their FDA approval in 2003.

Current devices

Currently, two models of drug-eluting stents are used. The first successful type released sirolimus (rapamycin), a powerful immunosuppressive and antiproliferative drug. Sirolimus, produced by the bacterium Streptomyces hygroscopicus, binds to the immunophilin FKBP-12. The resulting complex inhibits the mammalian target of rapamycin (mTOR), which has several effects, including preventing the cell from duplicating its genetic material; it blocks the cell cycle at the G₁→S transition. A sirolimus-eluting stent is produced by Cordis Corporation (Johnson & Johnson), and marketed under the name Cypher. This stent is made of stainless steel and uses a polymer as the carrier.

A second model uses paclitaxel, another antiproliferative drug. Derived from the yew tree, paclitaxel binds to and stabilizes microtubules. Without the dynamic framework provided by these components of the cytoskeleton, the cell cannot undergo mitosis and so is arrested at the M stage. The paclitaxel-eluting stent produced by Boston Scientific 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.

History

Heart attacks, or myocardial infarctions, 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. 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. The first procedural method to perform a type of open-heart surgery called coronary artery bypass graft (CABG) surgery, which uses a section of vein or artery from elsewhere in the body to bypass the diseased vessel. In 1977, Andreas Grüntzig introduced percutaneous transluminal coronary angioplasty (PTCA), in which a catheter was introduced through a peripheral artery and a balloon expanded to compress and crack the obstructive plaque.

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.. PTCA could only be used on limited scenarios, and the vessels had a high rate (30–40% in six months) of restenosis; additionally, 3% required emergency bypass surgery.. Dotter and Judkins had suggested using intraluminal prosthetic devices to maintain blood flow (in arteries of the leg) in 1964, and in 1986, Puel and Sigwart implanted the first stent in humans. 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.

Initial difficulties included blood clotting and occluding the stent in the hours or days after placement. Coating the stent with biologically inert substances like platinum or gold did not help. 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.

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. Soon thereafter, a series of trials of paclitaxel-eluting stents led to FDA approval of the Taxus stent in 2004.

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.

References

1. Michel, Thomas (2006) . "Treatment of Myocardial Ischemia". In Laurence L. Brunton, John S. Lazo, & Keith L. Parker (ed.). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed. ed.). New York: McGraw-Hill. p. 842. {{cite book}}: |edition= has extra text (help)CS1 maint: multiple names: editors list (link)
2. ^ Serruys, Patrick W. (2006-02-02). "Coronary-Artery Stents". New England Journal of Medicine. 354 (5): 483–495. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help) (extract)
3. ^ "New Device Approval — Cypher Sirolimus-eluting Coronary Stent". Food and Drug Administration. Retrieved 2006-07-22.
4. Krensky, Alan M. (2006) . "Immunosuppressants, Tolerogens, and Immunostimulants". In Laurence L. Brunton, John S. Lazo, & Keith L. Parker (ed.). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed. ed.). New York: McGraw-Hill. p. 1413. {{cite book}}: |edition= has extra text (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: multiple names: editors list (link)
5. Chabner, Bruce A. (2006) . "Antineoplastic Agents". In Laurence L. Brunton, John S. Lazo, & Keith L. Parker (ed.). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed. ed.). New York: McGraw-Hill. pp. 1352–1353. {{cite book}}: |edition= has extra text (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: multiple names: editors list (link)
6. ^ "New Device Approval — P030025 — TAXUS™ Express™ Paclitaxel-Eluting Coronary Stent System". Food and Drug Administration. 2004-09-09. Retrieved 2006-07-22.
7. Grüntzig, AR (1979-07-12). "Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty". New England Journal of Medicine. 301 (2): 61–68. Retrieved 2006-07-22. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help) (abstract)
8. ^ Baim, Donald S. (2005) . "Percutaneous Coronary Revascularization". In Dennis L. Kasper, Anthony S. Fauci, Dan L. Longo, Eugene Braunwald, Stephen L. Hauser, & J. Larry Jameson (ed.). Harrison's Principles of Internal Medicine (16th ed. ed.). New York: McGraw-Hill. pp. 1459–1462. {{cite book}}: |edition= has extra text (help)CS1 maint: multiple names: editors list (link)
9. Dotter, Charles T. (1964). "Transluminal Treatment of Arteriosclerotic Obstruction". Circulation. 30: 654–670. Retrieved 2006-07-22. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help) (abstract)

See also

• Fischetti, Mark (2006). "Vascular Stents: Expanding Use". Scientific American: 94. {{cite journal}}: Unknown parameter |month= ignored (help) (subscription required)