Drug-eluting stent: Difference between revisions
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===Alternative drugs=== |
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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. [[Abbott Laboratories|Abbott]] 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.<ref name="Abbott ZoMaxx">{{cite web |
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| url = http://www.abbott.com/global/url/content/en_US/30.20.50:50/general_content/General_Content_00024.htm |
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| title = Vascular Devices| accessdate = 2006-07-23| publisher = [[Abbott]]}}</ref> 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,<ref name="NEJM review" /> also uses phosphorylcholine to carry the zotarolimus was approved for use in Europe in 2005 is now close to U.S. FDA approval<ref name="StarTribune">{{cite web |
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| url = http://www.startribune.com/535/story/1476560.html |
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| title = FDA advisers OK Medtronic stent| accessdate = 2007-10-10| publisher = [[Star Tribune]]}}</ref> |
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Clinical trials are currently examining two stents carrying [[everolimus]],<ref name="NEJM review" /> an immunosuppressant that like sirolimus is used to prevent organ rejection.{{Fact|date=February 2008}} [[Guidant]], which has the exclusive license to use everolimus in drug-eluting stents, is the manufacturer of both stents. This Guidant business has subsequently been sold to Abbott Labs.<ref>{{cite web |url=http://www.abbott.com/global/url/pressRelease/en_US/60.5:5/Press_Release_0309.htm |title=Abbott Completes Acquisition of Guidant Vascular Business |accessdate=2007-01-12 |format= |work= }}</ref> The Champion stent uses a bioabsorbable polylactic acid carrier on a stainless steel stent.<ref name="FUTURE">{{cite journal |
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| 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 |
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| journal = [[Circulation (journal)|Circulation]] | volume = 109 | issue = | pages = 2168—2171 | doi = 10.1161/01.CIR.0000128850.84227.FD | id = PMID 15123533 |
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}}</ref><ref name="Guidant Champion">{{cite web |
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| url = http://www.guidant.com/news/400/web_release/nr_000459.shtml| title = Guidant News Release — April 5, 2004| accessdate = 2007-07-23| date = [[2004-04-05]] |
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| publisher = [[Guidant]] |
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}}</ref> In contrast, its Xience stent uses a durable (non-bioabsorbable) polymer on a cobalt stent.<ref name="Guidant Xience">{{cite web |
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| url = http://www.guidant.com/news/500/web_release/nr_000551.shtml| title = Guidant News Release — June 22, 2005| accessdate = 2006-07-23 |
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| date = [[2005-06-22]]| publisher = [[Guidant]] |
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}}</ref> |
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===The introduction of drug eluting stents=== |
===The introduction of drug eluting stents=== |
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Revision as of 01:03, 12 March 2008
A drug-eluting stent is a coronary stent (a scaffold) placed into narrowed, diseased coronary arteries that slowly releases a drug to block cell proliferation. This prevents scar-tissue–like growth 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.
Drug-eluting stents have been shown to be superior to traditional stents ("bare-metal stents") in reducing short-term complications.[citation needed] Their long term effectiveness compared to traditional stents or coronary bypass grafting is under scrutiny by the FDA.[1]
History
Early interventional cardiology technologies
The first procedural method to treat blocked coronary arteries was 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), also called balloon angioplasty, in which a catheter was introduced through a peripheral artery and a balloon expanded to compress and crack the obstructive plaque.[2]
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.[3] 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.[3] Dotter and Judkins had suggested using prosthetic devices inside arteries to maintain blood flow (in arteries of the leg) in 1964,[4] and in 1986, Puel and Sigwart implanted the first stent in humans.[5] 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 (those done via needle-puncture rather than incision) by 1999.[5]
Initial difficulties included blood clotting and occluding the stent in the hours or days after placement.[3] Coating the stent with biologically inert substances like platinum or gold did not help.[5] Eventually, using high balloon pressures to tightly fix the stent against the vessel and administering aspirin and another inhibitor of platelet aggregation (usually ticlopidine or clopidogrel) as anticoagulants were established; these changes eliminated most of the difficulty with in-stent thrombosis.[5][3]
The introduction of drug eluting stents
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, analogous 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 to ensure a sufficient concentration 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.[5] Soon thereafter, a series of trials of paclitaxel-eluting stents led to FDA approval of the Taxus stent in 2004.[6]
Indications
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 in cases of in-stent restenosis in prior stents.[5]
Contraindications
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Alternatives
Coronary artery bypass surgery Differences between outcomes with stenting and with coronary bypass grafting (CABG) are a point of controversy. Some studies suggest CABG is superior in multivessel (two or more diseased arteries) coronary artery disease (CAD) as regards a combined endpoint measure of death, myocardial infarction and repeat revascularization.[7] Other studies, including the ARTS II registry, suggest that drug-eluting stenting is not inferior to coronary bypass for treatment of multivessel coronary disease. In all comparison studies of stenting vs. bypass surgery, it is worth noting that only a small minority of patients with multivessel coronary disease have been eligible for inclusion in the studies, and that for most patients, clinical judgement by experienced operators suggests that one or the other approach is preferred.
Risks
In the last several years, drug-eluting stent use has become increasingly 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.
Risks due to cardiac catheterization
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 hematoma.[citation needed]
Coronary artery perforation
Rarely, a coronary artery can be perforated while the catheter is advanced or during stent placement.[3]
Stent thrombosis
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;[3] aspirin must be taken for life.[5]
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.[5] Both sirolimus and paclitaxel-eluting stents are associated with a small but statistically higher risk of thrombosis after the first year, compared to bare metal stents. Although this risk is still small, fatality results in one-third of patients who develop late thrombosis.[8] This risk is offset by drug-eluting stents' markedly reduced risk of restenosis and its complications including myocardial infarction. A meta-analysis concluded "the risks of mortality associated with drug-eluting and bare-metal stents are similar." The advantage of drug-eluting stents is in reduction of restenosis.[citation needed]
Whether sirolimus or paclitaxel-eluting stents are measurably different in their outcomes is a topic of great interest, including to the marketing departments of the manufacturers themselves. Analyses favoring one or the other stent have been advanced. The differences, if any, between the two devices are small. [9]
Allergic reaction
Rarely, a type of allergic reaction to the drug may occur; episodes of fatality have been reported.[10]
Design
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 polymer, although phosphorylcholine or ceramics are also being researched.[5] Different carriers release the loaded drug at different rates.
Controvery
Utilization of drug-eluting stents and market-share of the various stent manufacturers has fluctuated substantially since the introduction of these devices to the marketplace[11]. In the context of these changes in a >$5Billion market, opinions are often passionate, and sometimes are undoubtedly also affected by perspective and interests.
Coronary stents are often used in clinical scenarios not included in the FDA-label indications for the devices,[12] [13] and this has been a topic of controversy. Two studies found that about half of patients received stents for unapproved reasons, with worse outcomes for the patients in both studies. Some take this as evidence for overutilization of stents; others point to the frequency with which real patients have clinical problems which do not fit into the highly restrictive criteria around which a research study was built.
Bioresorbable stents
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 magnesium alloy–based stent has been tested in animals, though there is currently no carrier for drug elution.[14] 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[15] and paclitaxel[16] have been used as eluted drugs.
References
- ^ "US FDA/CDRH: FDA Statement on Coronary Drug-Eluting Stents". Retrieved 2008-02-25.
- ^ Grüntzig, AR (1979-07-12). "Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty". New England Journal of Medicine. 301 (2): 61–68. PMID 449946. Retrieved 2006-07-22.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ a b c d e f Baim, Donald S. (2005) [1958]. "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) - ^ Dotter, Charles T. (1964). "Transluminal Treatment of Arteriosclerotic Obstruction". Circulation. 30: 654–670. PMID 14226164. Retrieved 2006-07-22.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) (abstract) - ^ a b c d e f g h i Serruys PW, Kutryk MJ, Ong AT (2006). "Coronary-artery stents". N. Engl. J. Med. 354 (5): 483–95. doi:10.1056/NEJMra051091. PMID 16452560.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ "New Device Approval - P030025 - TAXUS™ Express2™ Paclitaxel-Eluting Coronary Stent System". Retrieved 2008-02-25.
- ^ Hannan EL, Wu C, Walford G; et al. (2008). "Drug-eluting stents vs. coronary-artery bypass grafting in multivessel coronary disease". N. Engl. J. Med. 358 (4): 331–41. doi:10.1056/NEJMoa071804. PMID 18216353.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Bavry AA, Kumbhani DJ, Helton TJ, Borek PP, Mood GR, Bhatt DL (2006). "Late thrombosis of drug-eluting stents: a meta-analysis of randomized clinical trials". Am. J. Med. 119 (12): 1056–61. doi:10.1016/j.amjmed.2006.01.023. PMID 17145250.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Stettler C, Wandel S, Allemann S, Kastrati A, Morice MC, Schömig A, Pfisterer ME, Stone GW, Leon MB, de Lezo JS, Goy JJ, Park SJ, Sabaté M, Suttorp MJ, Kelbaek H, Spaulding C, Menichelli M, Vermeersch P, Dirksen MT, Cervinka P, Petronio AS, Nordmann AJ, Diem P, Meier B, Zwahlen M, Reichenbach S, Trelle S, Windecker S, Jüni P (2007). "Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis". Lancet. 370 (9591): 937–48. doi:10.1016/S0140-6736(07)61444-5. PMID 17869634.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T, Mihalcsik L, Tespili M, Valsecchi O, Kolodgie FD (2004). "Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious?". Circulation. 109 (6): 701–5. doi:10.1161/01.CIR.0000116202.41966.D4. PMID 14744976.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ http://www.midwestbusiness.com/news/viewnews.asp?newsletterID=15086
- ^ Win HK, Caldera AE, Maresh K, et al (2007). "Clinical outcomes and stent thrombosis following off-label use of drug-eluting stents". JAMA 297 (18): 2001–9. doi:10.1001/jama.297.18.2001. PMID 17488965.
- ^ Beohar N, Davidson CJ, Kip KE, et al (2007). "Outcomes and complications associated with off-label and untested use of drug-eluting stents". JAMA 297 (18): 1992–2000. doi:10.1001/jama.297.18.1992. PMID 17488964.
- ^ Heublein, B. (2003). "Biocorrosion of magnesium alloys: a new principle in cardiovascular implant technology?". Heart. 89: 651–656. PMID 12748224. Retrieved 2006-07-23.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Tsuji, T. (2003). "Biodegradable stents as a platform to drug loading". International Journal of Cardiovascular Interventions. 5 (1): 13–6. PMID 12623560.
{{cite journal}}:|access-date=requires|url=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Vogt, Felix (2004). "Long-term assessment of a novel biodegradable paclitaxel-eluting coronary polylactide stent". European Heart Journal. 25: 1330–1340. PMID 15288161. Retrieved 2006-07-22.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help)
Further reading
- Fischetti, Mark (2006). "Vascular Stents: Expanding Use". Scientific American: 94.
{{cite journal}}: Unknown parameter|month=ignored (help) (layperson overview, subscription required) - Serruys, Patrick W. (2006-02-02). "Coronary-Artery Stents". New England Journal of Medicine. 354 (5): 483–495.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help) (journal review article, subscription required)
External links
