DALLAS — About a year from now, in 2007, there may be as many as six new drug-eluting coronary stents on the U.S. market.
Although none will likely improve on the efficacy or safety of the two drug-eluting stents now available—the sirolimus-eluting (Cypher) and paclitaxel-eluting (Taxus) stents—the new models will offer improved deliverability and increased competition, which might produce downward cost pressure in the coronary stent market, Dr. Gregg Stone said at the annual scientific sessions of the American Heart Association.
“All of the studies [of the new stents] are noninferiority trials,” he said. No studies are designed or powered to show that a new stent is better than the Taxus or Cypher models.
Dr. Stone reviewed the six new stents and their development status. Five feature sirolimus-like drugs, two of which use the same drug, ABT-578, which was recently renamed zotarolimus. The sixth stent uses paclitaxel.
Zotarolimus is contained in a phosphorylcholine polymer on Medtronic's Endeavor stent. The underlying stent is made from cobalt and has thin struts that make it very radioopaque, flexible, and deliverable, said Dr. Stone, director of research and education at the Center for Interventional Vascular Therapy, Columbia University, New York.
Three clinical studies, involving a total of more than 1,500 patients, have been completed with the stent. A fourth study, which is still in progress, is comparing the Endeavor with the sirolimus-eluting Cypher stent and involves another 1,500 patients.
So far, late loss rates with the Endeavor stent have been about 0.6 mm, which is substantially higher than the 0.2 mm or less in three major Cypher studies and the 0.30− to 0.35-mm rate seen in three major trials with the Taxus paclitaxel-eluting stent.
Despite this, clinical measures of restenosis have shown small differences between the Endeavor stent and those now on the market.
The target lesion revascularization rate, for example, was about 4%–5% in the sirolimus- and paclitaxel-eluting stent studies, and about 6% in the Endeavor studies.
One reason for this “big difference physiologically and small difference clinically” is that coronary arteries can accommodate some degree of late loss, Dr. Stone said. One recent analysis suggests that a late loss of up to 0.55 mm does not produce much clinical effect, although the incidence of adverse clinical outcomes rises linearly as the late loss rate increases from 0.55 to 1 mm and exponentially as it increases above 1 mm.
“The Endeavor stent sits at the cusp” with a late-loss rate of about 0.6 mm,” Dr. Stone said.
The second coronary stent using zotarolimus is the Zomaxx device made by Abbott. It is similar to the Endeavor except that it contains a second phosphorylcholine-polymer coat on top of the drug layer. The cap-coat is designed to control the elution of zotarolimus and allows for a variety of elution profiles.
The formulation used in the clinical studies releases about 75% of the drug in the first 10 days after placement and about 100% in 30 days, an elution profile similar to that of sirolimus in the Cypher stent. By comparison, the Endeavor stent releases 75% of its drug in the first 2 days of placement and about 100% in 10 days.
The Zomaxx stent is based on the Trimaxx bare-metal stent, a thin-strut, radioopaque device that is very flexible and deliverable, Dr. Stone said.
There are two clinical trials underway with the Zomaxx stent, one in Europe that will enroll about 400 patients and a second in the United States that has been designed as the pivotal trial and will enroll almost 1,700 patients.
Everolimus is another sirolimus analogue, and is used on Guidant's Xience V stent, which is composed of the Multi-Link Vision coronary stent and a thin, bioabsorbable polymer.
Everolimus was first used on a different stent, the Champion, but it tended to fracture and was therefore replaced. Combined angiographic outcomes data suggest that everolimus-releasing stents produce less than 0.2 mm late loss, which would make them as good as the sirolimus-eluting stent.
A European study with about 300 patients is underway, as is a pivotal U.S. study that will enroll almost 1,400 patients.
The fourth sirolimus-like agent, biolimus A9, is used on the Biomatrix stent, which is made by Biosensors and licensed to Devax.
Two major trials with this stent are scheduled to start this year. A European trial is slated to enroll about 1,700 patients, and a trial in the United States will enroll more than 1,400 patients.
Devax is also testing clinically the first coronary stent to have been designed for use in a coronary bifurcation, the Axxess Plus.