Things just mesh: making stents even better at keeping arteries open.Fatty deposits on the insides of blood vessels Blood vessels
Tubular channels for blood transport, of which there are three principal types: arteries, capillaries, and veins. Only the larger arteries and veins in the body bear distinct names. pile up less obviously than in a bulging belly or widening hips, yet in some ways they carry as much weight. These tiny products of the process called atherosclerosis atherosclerosis (ăth'ərōsklərō`sĭs): see arteriosclerosis.
or hardening of the arteries can block blood flow and oxygen to the heart, the brain, or other parts of the body.
After using a variety of techniques to clear blocked arteries, physicians now commonly insert metal-mesh tubes called stents into arteries to hold them open and prevent loose bits of the fatty plaque from closing the vessel again or getting swept into the bloodstream, where they can obstruct ob·struct
To block or close a body passage so as to hinder or interrupt a flow.
ob·structive adj. other blood vessels.
Cardiologists credit stents with improving the safety of artery-clearing procedures and boosting the percentage of blood vessels that stay open afterward. Because of this success, physicians are now investigating whether stents can be used more widely. For example, the tubes might be inserted into blood vessels narrower than those treated today and into people so sick that they now receive major surgery to replace and bypass blocked vessels. What's more, stents may find a role in blood vessels other than those servicing the heart. With each potential application of stents, however, the risks and benefits must be reassessed.
Problems identified in current applications of the devices provide several obstacles to broadening their use. Some, stents trigger immune inflammation, and up to a third of them reclog--a process called restenosis--within a few months after their insertion. Restenosis is typically marked by chest pain, as blood flow is impaired and the heart protests a lack of oxygen. Doctors treat restenosis either by performing additional artery-clearing procedures or by open-heart surgery open-heart surgery
Any surgical procedure opening the heart and exposing one or more of its chambers, most often to repair valve disease or correct congenital heart malformations (see congenital heart disease). to bypass the blocked vessel. Such repeat operations are expensive, and recovery from them can be difficult for patients who are already ill.
"If we had the promise of a stent with a low risk of restenosis, we could treat difficult atherosclerotic atherosclerotic
pertaining to atherosclerosis. lesions more confidently and probably send fewer people to bypass surgery Bypass surgery
A surgical procedure that grafts blood vessels onto arteries to reroute the blood flow around blockages in the arteries (arteriosclerosis). ," notes Alan Heldman Alan W. Heldman, M.D. (1962-) is an American interventional cardiologist.
Heldman graduated from Harvard College, University of Alabama School of Medicine, and completed residency and fellowship training at Johns Hopkins University School of Medicine. of Johns Hopkins University School of Medicine The Johns Hopkins University School of Medicine, located in Baltimore, Maryland, USA, is a highly regarded medical school and biomedical research institute in the United States. in Baltimore.
To develop a more long-lasting treatment, scientists are coating existing stents with polymers or gels containing drugs that block cell growth. "This is an exciting time for the whole field," Heldman says.
Doctors attack atherosclerois to prevent it from triggering heart disease, one of the leading causes of death in the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. . Which treatment they choose depends on the severity of the artery clogging, often detected with angiograms, which are x-ray images of blood vessels. People with mild atherosclerosis may receive only medications designed to prevent blood clots Blood Clots Definition
A blood clot is a thickened mass in the blood formed by tiny substances called platelets. Clots form to stop bleeding, such as at the site of cut. and cholesterol-lowering drugs to block any further fatty buildup inside arteries. In people who have severe blockages in vessels serving the heart, cardiologists typically perform surgery to bypass the diseased arteries.
Since the early 1980s, physicians have used an intermediate procedure to treat people with moderate atherosclerosis. In this process, called angioplasty angioplasty (ăn`jēōplăs'tē), any surgical repair of a blood vessel, especially
balloon angioplasty or percutaneous transluminal coronary angioplasty, a treatment of coronary artery disease. , a surgeon threads a tiny balloon inside an artery and inflates it, flattening the fatty deposits that narrow the artery. In the 1990s, doctors doing angioplasty started implanting a stent to improve the success of the procedure. For example, after Vice President Richard Cheney experienced chest pain in November 2000, he received a stent during angioplasty. Today, between 70 and 90 percent of people undergoing angioplasties get stents.
Recent studies have shown that the success rate for angioplasty is rising, even though physicians have been treating sicker and older patients than ever before. According to according to
1. As stated or indicated by; on the authority of: according to historians.
2. In keeping with: according to instructions.
3. researchers, most of that success is due to the widespread use of stents (SN: 2/3/01, p. 72).
In response to such findings, doctors are starting to treat severe atherosclerosis with angioplasty and a stent instead of bypass surgery. In the April 12 NEW ENGLAND JOURNAL OF MEDICINE The New England Journal of Medicine (New Engl J Med or NEJM) is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It is one of the most popular and widely-read peer-reviewed general medical journals in the world. , an international team of researchers reported that each technique offers about the same degree of protection against death, stroke, and heart attack among people eligible for either procedure.
Angioplasty and a stent provided the less expensive approach but were more likely than bypass surgery to eventually lead to additional angioplasty or a follow-up round of bypass surgery, says study leader Patrick W. Serruys of the Academisch Ziekenhuis Rotterdam Dijkzigt in Rotterdam, the Netherlands. If restenosis in stents were less common, angioplasty with stents might become the preferred treatment for many people otherwise slated for open-heart surgery, he says.
"Some things get to be trendy--used widely just because they are new--but I don't think that's the case with stents," says David O. Williams of Brown University in Providence, R.I. "The more we look, the better [stents' performance] gets."
The current problems arise because a newly implanted stent doesn't stay bare for long. Eventually, the metal surface is covered by a thin layer of epithelial cells Epithelial cells
Cells that form a thin surface coating on the outside of a body structure.
Mentioned in: Corneal Transplantation , which are the normal lining of blood vessels. The stent is thereby incorporated into artery walls, resembling steel bars embedded in concrete.
If healing stops there, restenosis is unlikely. However, sometimes the process goes into overdrive, causing smooth muscle cells from inside the blood-vessel wall to multiply and pile up inside the stent.
There are other causes of restenosis. The original problem of atherosclerosis can return, with fatty plaques building up inside the stent. Also, the stent can irritate the blood vessel blood vessel
An elastic tubular channel, such as an artery, a vein, a sinus, or a capillary, through which the blood circulates.
n the network of muscular tubes that carry blood. , prompting white blood cells White blood cells
A group of several cell types that occur in the bloodstream and are essential for a properly functioning immune system.
Mentioned in: Abscess Incision & Drainage, Bone Marrow Transplantation, Complement Deficiencies to swarm to the site. This can exacerbate atherosclerosis.
In large blood vessels with short blockages, less than 10 percent of stents clog. In small vessels, that rate can be more than 30 percent. Not all clogs in stents are large enough to dangerously block blood flow. Overall, about 12 to 15 percent of people who undergo angioplasty including a stent will need a follow-up procedure because of severe blockage. Because the stents are hard to spot with common imaging techniques, putting in another stent or performing bypass surgery can be tricky.
For these reasons, scientists and medical-device companies would like to develop stents resistant to restenosis. One approach is to coat stents with drugs. So far, drug-coated stents "look more promising than anything else we've seen," says Peter Fitzgerald For the Irish Garda deputy police commissioner and UN investigator into the Rafik Hariri assassination, see .
Peter G. Fitzgerald (born October 20, 1960) was the junior United States Senator from Illinois from 1999 until 2005. He is a member of the Republican Party. , a cardiologist Cardiologist
Doctor who specializes in diagnosing and treating heart diseases.
Mentioned in: Electrophysiology Study of the Heart, Lithotripsy
a physician who specializes in the diagnosis and treatment of heart disease. at Stanford University Stanford University, at Stanford, Calif.; coeducational; chartered 1885, opened 1891 as Leland Stanford Junior Univ. (still the legal name). The original campus was designed by Frederick Law Olmsted. David Starr Jordan was its first president. .
In early September at the European Society of Cardiology The European Society of Cardiology (ESC) represents more than 50,000 cardiology professionals across Europe and the Mediterranean. Its mission is to reduce the impact of cardiovascular disease in Europe. Annual Congress in Stockholm, an international team of researchers reported tests of a stent coated with a polymer that releases sirolimus, an immune-suppressing drug that slows cell growth. The sirolimus coating boosted angioplasty success rates. After about 7 months, only 4 of the 120 patients who received a drug-coated stent had died, suffered a heart attack, developed blood clots, or needed a follow-up heart procedure. After the same amount of time, 32 of the 118 people with a bare-metal stent had experienced one of those adverse events. Researchers didn't spot restenosis in angiograms of any patient implanted with the drug-coated stent, which is made by Cordis, a Johnson and Johnson company in Miami Lakes, Fla.
Cook, a company headquartered in Bloomington, Ind., is testing metal stents coated directly with the anticancer drug anticancer drug
anticancer drug Chemotherapeutic, see there paclitaxel paclitaxel /pac·li·tax·el/ (pak?li-tak´sel) an antineoplastic that promotes and stabilizes polymerization of microtubules, isolated from the Pacific yew tree (Taxus brevifolia); . Like most anticancer drugs Anticancer Drugs Definition
Anticancer, or antineoplastic, drugs are used to treat malignancies, or cancerous growths. Drug therapy may be used alone, or in combination with other treatments such as surgery or radiation therapy. , paclitaxel kills dividing cells, a process that in this case might prevent smooth muscle cells within an artery from overgrowing a stent.
In a study of 177 people receiving either bare-metal or paclitaxel-coated stents, 27 percent of the bare stents narrowed by more than half within 6 months. In contrast, 12 percent of stents coated with a low dose of the drug and just 4 percent of stents with high-dose paclitaxel were blocked to this degree.
The company reports that the buildup inside the stents was least in the high-dose paclitaxel stents, slightly more in the low-dose stents, and most pronounced in the bare stents. The company presented these results in Washington, D.C., at a September meeting on transcatheter cardiovascular therapeutics.
This month at the annual meeting of the American Heart Association American Heart Association (AHA),
n.pr a national voluntary health agency that has the goal of increasing public and medical awareness of cardiovascular diseases and stroke, and thereby reducing the number of associated deaths and disabilities. in Anaheim, Calif., researchers working with the Cook stent reported results from a trial of 192 European patients. In this study, 21 percent of the bare-metal stents narrowed by more than half after surgery. The researchers tested several doses of paclitaxel released from the stents. The more paclitaxel was released, the more benefit.
Just 3.1 percent of the stents releasing the highest dose of paclitaxel narrowed by half within 6 months. There was no reported side effect from the drug. The average percentage of restenosis in each stent after 6 months was 34 percent in the group treated with bare-metal stents and 14 percent in those people implanted with the high-dose paclitaxel stent.
In another study released at the September meeting, Ivan De Scheerder of University Hospitals in Leuven, Belgium, reported success in placing paclitaxel-coated stents inside already implanted, bare-metal stents that had repeatedly reclogged. Six months after doctors implanted new stents inside the old ones in 21 patients, there was no sign of restenosis in any patient.
In a less formal setting, Boston Scientific The Boston Scientific Corporation (NYSE: BSX) (abbreviated BSC), is a worldwide developer, manufacturer and marketer of medical devices whose products are used in a range of interventional medical specialties, including interventional cardiology, peripheral interventions, Corp., a Boston-based company that makes stents, recently reported to stock analysts promising results from an initial trial of a stent coated with a paclitaxel-containing polymer. Larger studies of these paclitaxel-releasing stents are now under way.
These "are significant benefits," says Fitzgerald. "There's not a lot in our armament that's gotten people this excited. I think we'll adopt coated stents like crazy." Still, there may yet be unexpected roadblocks, Fitzgerald and other researchers caution.
While cardiologists' celebration over the early results with coated stents is understandable, says Renu Virmani of the Armed Forces Institute of Pathology Armed Forces Institute of Pathology A section of the US military which provides consultations, reference atlases and educational programs for pathologists in Washington, D.C., "this is a premature celebration. We need to wait for the long term, perhaps 2 or 3 years."
Virmani bases her caution in part on history. In the late 1990s, researchers showed that stents impregnated im·preg·nate
tr.v. im·preg·nat·ed, im·preg·nat·ing, im·preg·nates
1. To make pregnant; inseminate.
2. To fertilize (an ovum, for example).
3. with radioactive elements are effective in reducing the buildup of new cells inside the stent. Over the past year or so, however, several research teams have shown limits to the proposed benefits.
The radiation kills cells within the stent, preventing restenosis, but it also damages tissue upstream and downstream of the mesh tube, researchers have discovered. In the process of healing that damage, cells in these areas grow rapidly, narrowing the blood vessels at either end of the stent in what scientists have called a "candy-wrapper" effect. So far, there is no sign of such an effect around drug-coated stents.
Virmani says that her first reservation about these devices is that "once the drug disappears, there will be no benefit." Animal trials of the sirolimus-coated stent suggest that the drug lasts for 15 or 45 days, depending on the formulation.
Virmani's also concerned that the drug coatings will slow the incorporation of the stent within the vessel's walls. The thin covering of epithelial cells reduces the risk that a metal stent will trigger blood clotting blood clotting, process by which the blood coagulates to form solid masses, or clots. In minor injuries, small oval bodies called platelets, or thrombocytes, tend to collect and form plugs in blood vessel openings. , she says.
This potential effect on blood clotting "is a theoretical concern, not yet seen," says Fitzgerald. However, he agrees that researchers should carefully track the incidence of blood clots.
"Restenosis rarely kills anybody. They walk into the hospital and say, `Doc, my chest is hurting,'" Fitzgerald says. Their restenosis can then be treated.
On the other hand, blood clots can break off, clog an artery, and cause a heart attack or stroke without warning. Fitzgerald says, "We really have to look carefully at these studies and make sure what we're so excited about holds up over the long term."
Prompted in part by the excitement over the success of drug-coated stents, research into next-generation devices is moving ahead quickly. Those are being made with new coatings or new materials.
In one approach, researchers are changing the way that stents release a drug. Right now, chemicals associated with the stent start entering the blood as soon as doctors put the device into the body. But overactive o·ver·ac·tive
Active to an excessive or abnormal degree: an overactive child.
o growth of smooth muscle cells and inflammation are most likely to start a few days later. If a drug instead could remain bound for a day or two after implantation, restenosis might be more effectively deterred, Fitzgerald says.
Given the need for the stent to become incorporated within the blood vessel, other researchers are trying to find materials that will block the growth of smooth muscle cells but let epithelial cells grow normally.
Robert J. Levy of the Children's Hospital of Philadelphia The Children's Hospital of Philadelphia is one of the largest and oldest children's hospitals in the world. "CHOP" has been ranked as the best children's hospital in the United States by U.S. News & World Report and Child Magazine in recent years. and his colleagues are developing stents with a coating containing genes that, if absorbed into nearby cells, might slow atherosclerosis. "Because the stents are implanted at areas of major disease activity, it's an opportunity to treat local disease beyond the mechanical benefit of keeping the artery open," he says.
Last November, Levy and his colleagues reported that they could use stents to deliver marker genes to cells in blood vessels (SN: 11/18/00, p. 325). These genes had no particular function but were easy to detect in cells that took them up, he explains. The researchers haven't yet decided which genes might provide effective therapy.
The stent coating that Levy used in his initial studies triggered some inflammation. At the American Heart Association meeting this month, Levy reported tests that used a stent coating of collagen, the rubbery tissue of connective tissue and bones. It delivered genes to the blood vessel immediately around the stent while inducing little inflammation.
Stents themselves are the targets for improvements. Since the chance of restenosis is highest in the first several months after surgery, researchers have tried to develop stents that will degrade TO DEGRADE, DEGRADING. To, sink or lower a person in the estimation of the public.
2. As a man's character is of great importance to him, and it is his interest to retain the good opinion of all mankind, when he is a witness, he cannot be compelled to disclose after the blood vessel has healed from angioplasty. Getting materials that do this has been surprisingly difficult, however, because many of the biodegradable biodegradable /bio·de·grad·a·ble/ (-de-grad´ah-b'l) susceptible of degradation by biological processes, as by bacterial or other enzymatic action.
adj. stents have triggered immune responses and inflammation when tested in animals.
A new biodegradable stent seems to provoke less of an immune response. In the July 25, 2000 CIRCULATION, Hideo Tamai of the Shiga Medical Center for Adults in Moriyama, Japan, and his colleagues reported that a stent made from a biodegradable polymer was safe and effective in patients who were undergoing angioplasty.
At the American College of Cardiology The American College of Cardiology (ACC) is a nonprofit medical association established in 1949 to educate, research and influence health care public policy. The president for the 2006–2007 year is Steven E. Nissen.  The organization has 39 chapters in the U.S. meeting in Los Angeles Los Angeles (lôs ăn`jələs, lŏs, ăn`jəlēz'), city (1990 pop. 3,485,398), seat of Los Angeles co., S Calif.; inc. 1850. last February, the team reported that 1 year after receiving a biodegradable stent, 7 of 36 patients showed signs of restenosis, about the same as in patients getting a traditional metal stent. The scientists plan to continue observing these patients to see how the new stents degrade and what the long-term consequences are.
A stent that will degrade over time is less likely than a metal tube to interfere with future angioplasty or bypass surgery, says Antonio Colombo of the Centro Cuore Columbus in Milan. With Tamai's work, he says, "a number of former problems have been resolved and a new approach to coronary stenting Coronary Stenting Definition
A coronary stent is an artificial support device used in the coronary artery to keep the vessel open.
Purpose is emerging."
Biodegradable stents could also serve as a platform for drug or gene delivery.
Overall, cardiologists are hopeful that drug-coated stents--and their successors--will address the serious problem of atherosclerosis even more safely and effectively than angioplasty has to date. "Drug-coated stents work, and our patients will see benefits," says Heldman. With cardiologists considering broad expansions of stents' widespread use today, he says, preventing restenosis is more important than ever.