Stent Technology: Where Weve Been, Where Were Going

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Newer-generation stents such as this Xience V from Abbott tend to be more flexibile and have better conformability than earlier generations.
Stent research builds on the challenges of yesterday to ensure tomorrow’s patients are better served.

The dawn of coronary angioplasty spearheaded a new era for interventional cardiologists and their patients. The excitement surrounding balloon angioplasty and bare-metal stent implantation, however, soon gave way to the realization that patients undergoing percutaneous coronary interventions with these devices developed in-stent restenosis and needed to be revascularized. Since then, manufacturers have sought to optimize the design, delivery and content of stents to minimize vessel damage and maximize healing.

The four major stent vendors in the U.S.—Abbott, Boston Scientific, Cordis Corporation and Medtronic—have incorporated various design elements in their stents in an effort to stem restenosis and thrombotic events, as well as effectively place the stent in difficult anatomic locations.

Compared with newer-generation stents, earlier versions were thicker and more rigid, often made from a slotted-tube design. Newer stents take advantage of lighter, stronger metals, such as cobalt chromium, and various modular strut designs that enable them to be thinner, stronger and more flexible. Today’s struts are roughly 80 microns thick, compared to 100 to 120 microns for earlier generations. The increased flexibility enables the stent to move smoothly through the tortuous coronary anatomy, creating as little trauma as possible. Despite their smaller and lighter stature, newer-generation stents have excellent radial strength to hold the vessel open. 

“Thinner struts and a more flexible design will allow less trauma upon delivery, better movement per se of the vessel and better healing over the top of the stent,” says Jason Fontana, PhD, senior director of marketing at Medtronic Cardiovascular. With less initial trauma, there is a better chance of reduced neointimal growth, or restenosis, and increased endothelialization.

The stent delivery system is an important component of the stenting procedure. The ease and flexibility of the delivery system are due to a number of different factors including material selection, balloon characteristics and the shaft design. “All of these things need to be developed in concert to maximize deliverability,” says Jamey Jacobs, divisional vice president and general manager for coronary products at Abbott Vascular. “There is a whole evolution of refinement of the delivery system that is a significant contributor to the overall performance of the product.”

Drugs and elution kinetics

To help reduce in-stent restenosis, manufacturers have added drugs to stents. Studies have generally shown that drug-eluting stents (DES) are more effective than bare-metal stents (BMS) in preventing coronary restenosis, but may predispose patients to stent thrombosis through incomplete tissue coverage of the stent struts. Manufacturers use various drugs, amounts and elution kinetics to achieve the widest therapeutic range in an effort to slow or stop restenosis and promote optimal healing.

The Taxus stent is coated with paclitaxel, while the other three FDA-approved DES use a “limus” analogue: Cypher elutes sirolimus, Xience V is coated with everolimus and the Endeavor has zotarolimus. Paclitaxel is a cytotoxic immunosuppressant, while the other three are cytostatic immunosuppressants. All four drugs have broad safety profiles and are released in a controlled fashion, allowing the smallest amount of drug possible on the stent. With the Xience V, for example, 80 percent of drug is released within 30 days. The other 20 percent is released within 90 days. “We consider this to be optimal for a drug-eluting stent system,” says Jacobs.

Endeavor elutes its drug within 28 days; Cypher and Taxus roughly within 90 days. What the different elution kinetics do is lead to differences in neointimal coverage and endothelialization. The faster the drug is released, the more chance there will be for increased neointimal growth. On the other hand, the faster the drug is gone, the better chance rapid endothelialization, or healing, takes place. Despite differences in elution kinetics, studies have shown that the rates of target lesion revascularization at nine months are similar for all four products.

A sneak peek: stents of tomorrow

In the U.S., all DES have durable polymers, which means they are on the stent for the length of its life. Recent research suggests that polymers could be associated with late and very late stent thrombosis. The hypothesis is that the polymers left behind could be leading to inflammation in the vessel, causing a lack of healing. Data supporting or refuting this theory are at present inconclusive. “Late stent thrombosis is something that has many different facets. It may be that a very benign, inert, nonthrombogenic durable polymer is safer than a bioabsorbable coating that goes away,” Jacobs says.

The polymer should be inert, with a low and decreasing inflammatory response. Mechanically, the polymer needs to consistently and accurately disperse the drug to the release kinetics of the design. It also needs to have exceptional durability so that it doesn’t crack or fracture upon delivery and deployment. “These polymers undergo exceptional strain as they are being deployed. And having a very thin polymer that is fracture resistant is very important,” Jacobs says. 

In the meantime, research is ongoing for the development of bioabsorbable polymers that will degrade within a six-month period, as well as nano-porous stents that don’t need polymers, but carry the drugs in fine pores within the stent.

Researchers also are working to develop fully bioabsorbable stents, which potentially address late or very late stent thrombosis. As one researcher said, “You can’t have late stent thrombosis if there is no late stent.” Biodegradable stents potentially allow the vessel to return to its natural state. Jacobs says that researchers have seen a restoration of the lumen to its natural size at two years and restoration of normal vasomotion in the ABSORB trial, which is studying Abbott’s bioabsorbable stent.

“The DES are still the primary tool for preventing restenosis, and we expect that the advancement of technology will soon resolve the drawbacks of currently available stents,” wrote Christodoulos Stefanadis, MD, and Konstantinos Toutouzas, MD, from Athens Medical School (J Am Coll Cardiol 2009;53:665-666).

All components of stents work in concert to promote healing as quickly as possible. The device itself and all its design elements, as well as the delivery system, are geared toward minimizing trauma upon deployment. The drug, drug kinetics and the polymer are involved with the safety and healing properties of the stent up to the one-year timeframe. The next phase is fully bioabsorbable stents that degrade over time, potentially alleviating problems with late and very late stent thrombosis. There is also ongoing research into various drug combinations that might be effective against restenosis. The path from the first balloon angioplasty to today has seen many improvements in stent design and delivery. The immediate future should see further refinement that increase patient safety, morbidity and mortality.