As drug-eluting stent (DES) technology continues to move forward, that progress increasingly points to a broadening range of applications. And paclitaxel, supplied by Angiotech Pharmaceuticals (Vancouver, British Columbia), can lay considerable claim to leading the way in the drug portion of this drug/device combination.

The first patient in a 60-patient trial to evaluate the use of a paclitaxel-coated stent to treat peripheral arterial disease (PAD) – as distinguished from use in the coronary arteries – was implanted with the Zilver PTX stent from Cook (Bloomington, Indiana) earlier this week at Stanford University Medical Center (Palo Alto, California).

Cook puts the trial clearly in the "landmark" category.

The company said the trial is the first in the U.S. to determine whether or not DES devices can have similar benefits, compared to those used to treat coronary arteries, in preventing restenosis in the peripheral vasculature.

William Hunter, MD, president and CEO of Angiotech, noted the "headway" that its paclitaxel drug product is making in the U.S.

"We believe Cook's data with the Zilver paclitaxel-deluting stent to treat the silent epidemic of PVD [peripheral vascular disease] will reinforce the consistent safety and superior efficacy of paclitaxel in reducing restenosis that we have seen previously in the coronary arteries."

Cook's Zilver PTX DES device was implanted in a woman, characterized as elderly, by a team of doctors led by Michael Dake, MD, professor and chairman of the department of radiology at the University of Virginia Health System (Charlottesville, Virginia). Dake is the national principal investigator.

While noting the success of DES devices in reducing reclogging of coronary arteries, Dake said that the success of DES technology is far from a "slam-dunk" in the peripheral arteries. "The proof is in the tasting," he told Medical Device Daily, while expressing the hope that the new application in the legs will replicate that produced in coronary uses.

He also noted key differences between coronary DES technologies.

The Zilver is a self-expanding, rather than a balloon-expandable, stent and therefore offers "unique mechanical challenges," Dake said. The device uses "some outer membrane to be sure the drug is constrained sufficiently to the stent scaffold not to lose any of the dose." Treatment is also for longer lesions, with the "trend" of success requiring a longer period of time to determine, perhaps up to nine months.

Dake was careful to avoid an "apples-to-oranges" comparison with coronary stenting, but said that stenting in the leg tends to see up to a 30% rate of restenosis. He called that "a good target to shoot for" in terms of computing hoped-for reductions with the Zilver.

He added the caveat: "All the animal studies in the world can't actively predict what will happen" in humans.

Expanding on the differences, Daniel Sze, MD, PhD, associate professor of radiology and principal investigator for Stanford's portion of the trial, noted that the challenges in treating leg arteries are greater. They are, for instance, much longer and wider than coronary arteries. And compared to the stiffness and "macaroni" size of a coronary stent, the DES placed in the woman's leg was about the size of a crayon and very pliable.

Dake noted also that the woman had undergone a previous round of therapy called surgical aortoilliac revascularization, "but still experienced pain after walking 1-1/2 miles."

In a statement, the Stanford Medical Center said it would take up to at least six months to determine if the patient was experiencing restenosis of the treated artery, but added: "[A] day after the stent was in place, she was already walking with greater ease."

The new trial primarily will focus on the safety of the Zilver PTX stent above the knee in the femoropopliteal artery, the major artery in the thigh, compared to standard PAD interventions, according to Charles McIntosh, MD, PhD, vice president of medical science and technology for the Cook Group.

Like the Taxus coronary DES stent from Boston Scientific (Natick, Massachusetts), the Zilver PTX is coated with the drug paclitaxel. But the stent does not use a polymer to bind the paclitaxel drug to the device, McIntosh told MDD.

He declined describing the specifics of the drug/device attachment method, citing that as proprietary information, but emphasized that the mechanism assures "close proximity" between drug and arterial wall.

And while also declining to discuss the company's pre-clinical data, McIntosh described these as indicating "good results."

Delivery for the leg application, he said, was similar to the system used in the delivery of bare-metal stents.

Cook sees completion of enrollment in the trial before the year is out, McIntosh said, with hoped-for launch of a Phase II trial in 100 patients in 2006. He added that the enrollments should be rapid given a continuing preference by patients for the DES technology.

While describing potential FDA clearance as "a moving target," he said it could be issued in the 2007-2008 range.

DES use to treat PAD is important since this illness affects more than 10 million American annually, according to Cook. PAD affects blood vessels that lead from the heart to other areas of the body such as the legs, feet and kidneys. When the blood vessels become blocked by buildup of fatty deposits, the initial results are pain while walking, and the continued blockage can result in gangrene and eventual amputation.

PAD is, according to Cook, "seriously under-diagnosed." Besides offering its own risks, symptoms of PAD indicate the increased risk of heart disease and stroke.

Cook terms itself "the world's largest privately held medical device manufacturer," and says it is developing a variety of technologies: stents and stent-grafts, catheters, wire guides, introducer needles and sheaths, embolization coils, medical biomaterials, vena cava filters, implanted cardiac lead extraction equipment and other minimally invasive medical devices.

Stanford University Medical Center provides research, medical education and patient care at its three institutions: Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital.