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