CDU Senior

Two powerhouse medical device companies reported significant developments in their cardiovascular stent programs in mid-July, with an emphasis on new, lighter materials. Guidant (Indianapolis, Indiana) gained U.S. approval for a significant new stent and Medtronic (Minneapolis, Minnesota) said it has begun a second trial for its Endeavor drug-eluting stent platform.

With the belief that thinner is better, Guidant disclosed that the newest generation to its stent program, the Multi-Link Vision Coronary Stent System, received FDA approval. The approval marks the introduction of the first in a new class of coronary stents in the U.S. that use a cobalt chromium alloy which allows for a thinner strut design and a lower profile. The company said this would enable physicians to more easily access challenging coronary blockages, and Guidant plans to use the new stent technology in future therapy programs including drug-eluting stents and vulnerable plaque therapies.

"The Multi-Link Vision Stent System demonstrates [our] continued leadership in metallic stent design, with excellent acute performance and long-term clinical outcomes," said Dana Mead Jr., president of Guidant's Vascular Intervention division.

Mead told CDU's sister publication, Medical Device Daily, that the clinical data thus far has trended in such a way "that you would suspect that a thinner strut will cause less injury during deployment of the stent and therefore, can produce a better clinical outcome." While he acknowledged that there might not be a "huge bolus of clinical data out there that supports it," he said there is enough data out there "that people believe that thickness of struts could contribute in a [thicker] metallic stent frame to a higher restenosis rate."

U.S. approval was received for the device in 3.0 mm to 4.0 mm diameters and 8 mm to 28 mm lengths. The stent has demonstrated positive clinical results, with a six-month clinically driven target lesion revascularization (TLR) rate of 1.9%. TLR is defined as a repeat procedure at the original lesion site any time during the follow-up period.

"The six-month clinically driven TLR rate for the Multi-Link Vision stent is extremely promising," said Dean Kereiakes, MD, co-principal investigator for the study, chief executive officer of the Ohio Heart Health Center and medical director of The Lindner Center for Research & Education at The Christ Hospital (Cincinnati, Ohio). "The combination of cobalt chromium and the unique Vision stent design truly expands the treatment options available to interventional cardiologists and their patients."

According to Mead, one of the most important aspects of this new material is its versatility. "The issue with stainless steel is the only way that you can make it have the right level of radiopacity is just to make the strut thicker. What that did is that it limited it to some degree because you need to have that visibility in order for physicians to be able to see the stent appropriately when they're placing it and to promote accurate placement of the stent." By having thinner-walled stents, made possible by the cobalt chromium alloy, "you're able to get more preferable performance characteristics from the stent," he said. The Vision, he added, has a host of desirable characteristics. "It gets you to a thinner wall, with good radiopacity and gives you more flexibility with design which we believe will lead to better performance."

Mead said that the Vision will definitely be used as part of Guidant's drug-eluting stent platform, "at least for a first-generation product." He said he believes that the new stent design will bode well for the company once it begins participating in the drug-eluting stent market. "We believe that the results from the drugs will prove to be fairly similar and then the basis of competition will revert back to the ability to deliver these things in a predictable manner."

Guidant recently reintroduced the product in Europe after a voluntary product recall. The company launched the Vision stent in Europe in February, then pulled it from the market in late March after the stents became dislodged from the delivery system in what it said were a "limited number" of cases. The company said no patients were harmed as a result of the stents becoming dislodged. "We believe the changes that we made have actually enhanced the performance of the product," Mead said, adding that Guidant made a change in the manufacturing processes "to make the stent more secure on the [delivery] system."

According to Mead, the Vision will cost around $1,400, about a 30% premium over standard metallic stents currently on the market. He said the Vision, while at the top of Guidant's pricing pyramid, would not replace its other stent products. "This will provide us a portfolio of stents," he said, noting that the company will continue to sell the Zeta, Penta and Pixel lines. He added that Guidant expects to introduce the Multi-Link Mini-Vision, a small-vessel cobalt chromium stent, in Europe in the second half of this year, with a U.S. launch sometime early next year.

In another development reported nearly in tandem with the Guidant announcement, Medtronic Vascular (Santa Rosa, California), a division of Medtronic, said it has started the ENDEAVOR II pivotal clinical trial for its Endeavor drug-eluting stent. The trial will evaluate the safety and efficacy of the Endeavor stent and will support product approvals in various countries. The primary endpoint of the study is target vessel failure (TVF) at nine months.

The study will include about 1,200 patients enrolled at 96 hospitals in 21 countries throughout Europe, the Middle East, the Asia-Pacific region and Canada.

The study's first patient was enrolled and received an Endeavor drug-eluting stent on July 14 in a procedure that was performed at the Kerckhoff Klinik (Bad Nauheim, Germany) under the supervision of professor Christian Hamm, director of the department of cardiology.

"The start of this pivotal trial ahead of schedule demonstrates Medtronic's commitment to regaining its leadership position in coronary stents and represents an important step in our efforts to commercialize our drug-eluting stent in the European market in the latter part of 2004 and in the U.S. by the end of 2005," said Bill Hawkins, president of Medtronic Vascular. "If the stent meets our clinical expectations, it will provide a competitive alternative to other drug-eluting stents in the marketplace."

The Endeavor stent uses the drug ABT-578, a compound licensed by Medtronic from Abbott Laboratories (Abbott Park, Illinois). ABT-578 is designed to inhibit smooth muscle cell proliferation a key contributor to restenosis by blocking the function of the cell cycle regulatory protein, mTOR. By inhibiting the mTOR function, ABT-578 permits the cell to return to normal function vs. causing cell death.

Medtronic also licensed from Abbott rights to the phosphorylcholine (PC) coating technology, a polymer copy of the outside surface of a red blood cell, which mimics the structure of the natural cell membrane and is designed to reduce the body's response to implanted devices. The PC polymer is designed to serve as the "delivery matrix," which controls the elution or release of ABT-578 directly into the arterial wall.

The Endeavor uses Medtronic's new Driver stent, which has CE mark approval in Europe for treating large and small vessels. The Driver stent, much like Guidant's Vision, is composed of a cobalt-based alloy that is designed to be stronger and denser than the stainless steel used in other stents. The alloy also is designed to allow for thinner struts, resulting in a lower profile and better deliverability in the vessel without compromising radial strength and visibility. Medtronic estimates that the Driver stent will be approved in the U.S. by this fall.