Cardiovascular technologies have long been at the heart – one might say – of medical device development, and that arena recently has seen the emergence of two sub-sectors: drug-coated stents and septal occlusion devices. Interestingly, the two technologies offering a sharp contrast in purpose: Stent technology is intended to maintain an open supply of blood in the vasculature, while septal occlusion attempts to shut off unwanted movement of blood in the heart.

The use of drugs to decrease the rate of in-stent restenosis is seen as just one approach to the problem – with radiation entering the competition last year and gene therapy on a future horizon. Whatever the technological strategy, the intent is to maintain continued normal blood flow at the stent site by preventing the reclogging of tissue around it. While radiation has decreased the rate of restenosis, the drug/device combination has demonstrated near-zero results in the most recent reports of early clinical trials.

Thus far, Cordis (Miami Lakes, Florida), a unit of Johnson & Johnson (New Bunswick, New Jersey) is seen as having a substantial lead in bringing a drug/stent combination to market sometime next year. And in an attempt to play catch-up, Guidant (Indianapolis, Indiana) and Cook (Bloomington, Indiana) in late August set aside competitive concerns and formed an agreement to combine their efforts. Cook will have access to Guidant's stent technologies and will contribute to Guidant its polymer-free paclitaxel coating, with the drug coating itself licensed from Angiotech Pharmaceuticals (Vancouver, British Columbia).

When the pact was announced, John DeFord, PhD, Cook's president and CEO, said that the agreement was, in part, an effort to avoid patent battles between the two companies. However, Boston Scientific (Natick, Massachusetts) has raised its own legal challenge to the agreement, issuing a Notice of Dispute to the companies, saying that it and Cook – not Guidant – have the only right to commercialize stent products using Angiotech's paclitaxel coating. This has put Angiotech in the middle, with that company issuing a statement attempting to distance itself from the dispute.

In a similar approach, Implant Sciences (Wakefield, Massachusetts) and CardioTech International (Woburn, Massachusetts) in late August reported their own agreement to develop a drug-eluting stent – a stent that releases the drug rapamycin over a period of several months. Michael Szycher, MD, PhD, president and CEO of CardioTech, said this coating "is not just a coating – it is a microporous structure," using biodurable polymer, trade-named ChronoFlex. This, he said, provides for improved healing over time around the stent as a way to retard restenosis. Dr. Clara Bajgar, manager of medical device development at Implant Sciences, said that besides working on cardiovascular applications for the drug/device treatment, the company is developing applications such as drug-eluting stent grafts "with enhanced anti-restenotic properties for the treatment of abdominal aortic aneurysms."

Still another technology may enter the anti-restenosis effort with a report in late September from PharmaSonics (Sunnyvale, California), showing the reduction of in-stent restenosis via ultrasound, using its Intravascular Sonotherapy System following coronary stenting. At press time, the company said that early results of its SILENT trial, a Phase I registry of 1,200 patients, supported the results of its earlier SWING trial, which followed 450 patients. Ronald Caputo, MD, an interventionalist involved in the SWING trial at the cardio lab of St. Joseph's Hospital (Syracuse, New York), told Cardiovascular Device Update that it was still too early to draw conclusions, but that he saw the use of ultrasound as another weapon against restenosis both in angioplasty and in stenting and in treating peripheral vasculature.

The second emerging area – septal occluding devices – received a strong boost last month with FDA panel approvals for the occlusion devices being developed by NMT Medical (Boston, Massachusetts) and AGA Medical (Golden Valley, Minnesota). These systems offer less-invasive alternatives to surgery for plugging small holes in the heart that prevent its proper function. In infants, some of these congenital defects will prevent the child's growth and development and so must be closed fairly quickly. Other forms of septal holes may be asymptomatic initially but can result in serious heart failure in later years.

In an early September meeting, the FDA's Circulatory Systems Devices Panel voted to recommend approval of NMT's CardioSeal Septal Occlusion System for treatment of congenital ventricular septal defects of the heart, and to AGA Medical for its Amplatzer Septal Occluder (ASO) system for two indications in this area. The technical terms for AGA's applications are treatment of atrial septal defects (ASD) in secundum position and closure of the fenestration following a fenestrated fontan procedure.

Larry Haimovitch, president of Haimovitch Medical Technology Consultants (San Francisco, California), who follows the cardiovascular sector for CDU, said that the panel approvals "aren't going to dominate interventional cardiology news" when compared to the current market battles over stents – which he termed "stent wars." But he said that, with approval of expanded applications, the devices would address a fairly large population of people needing treatment for patent foramen ovales (PFOs), holes between the left and right atria, which do not close, allowing a reverse flow of blood. NMT has estimated a population of 80,000 to 90,000 in the U.S. with PFOs and a worldwide population of 450,000. Besides PFOs, other terms for these leakages of blood in the heart are PDA (patent ductus arteriosus), ASD (atrial septal defect) or VSD (ventricular septal defect). The CardioSeal system consists of an occluder, or closure, system and a catheter-assisted delivery device. It describes the occluder as an alloy framework on which polyester fabric is attached. The placement and attachment is made by means of what the company calls a Qwik Load loading system for delivering the occluder, which is then held in place by natural pressure. For its part, AGA describes its ASO device as a "self-expanding, self-centering, repositionable, double-disk" system comprised of nitinol metal braid with polyester patches sewn into the disks. It too is delivered by means of a catheter. Haimovitch noted that the ability to place these devices less invasively puts them at a clear advantage over standard surgical procedures.

Additionally, surgery often is not appropriate for older patients, so blood thinners are often used to reduce adverse events such as carotid stenosis or stroke. But Haimovitch pointed to increasing evidence that anticoagulation therapy may not offer as much benefit to these patients as previously believed and that, especially for active patients who are more subject to cuts and bruises, the use of blood thinners may result in excessive bleeding. "It appears [these] closure devices may provide a much better solution," he said.

Besides their specific cardiovascular applications, the devices may have broad potential uses in the neurological arena, especially in the reduction of stroke. NMT has indicated it has longer term plans for expanding to this sector. Supporting this, Haimovitch noted new research evidence indicating that up to 10% of strokes may have their basis in a septal defect of the heart. "That's really significant and unrecognized in the neurology community," Haimovitch said. "Now we have a pretty elegant solution from the interventional standpoint that seems to really solve the problem, as opposed to major open-heart surgery."

Medtronic to pay Boston Sci $169M

Based on a mid-September ruling by the U.S. District Court for the Northern District of California, Medtronic (Minneapolis, Minnesota) must pay Boston Scientific (Natick, Massachusetts) a $169 million damage award, plus costs and attorneys' fees related to their dispute over rapid-exchange balloon catheters and stent delivery systems. Medtronic said it agreed to stop selling its devices using the rapid-exchange system, a loss in sales that has been estimated at $190 million.

The halt in sales includes the S670, the S660 and the beStent stent delivery systems and the RIS balloon dilatation catheter using the rapid-exchange system. A Boston Scientific statement said, "The key features of the stent delivery system used in Medtronic's S7 rapid exchange product are identical to one found by the arbitration panel to be infringing." The arbitration panel determined that infringement this past July and set the $169 million infringement award. Medtronic said that the stents in this case will continue to be sold using over-the-wire delivery systems and that it will continue to market rapid-exchange catheters outside the U.S.

Both companies said they had attempted, but failed, to reach an alternative settlement in the dispute. Medtronic had contended that it had acquired the right to use the rapid-exchange perfusion system when it purchased the angioplasty business of C.R. Bard (Murray Hill, New Jersey).

Thoratec establishes Burnett fund

Cardiovascular device maker Thoratec (Pleasanton, California) has established a fund honoring Thomas Burnett Jr., who was killed in the terrorist-related crash of United Airlines Flight 93 in Pennsylvania Sept. 11. The Thomas E. Burnett Jr. Family Memorial Fund is a way of honoring Burnett, who was the company's senior vice president and chief operating officer. D. Keith Grossman, president and CEO of the company, said the fund has been launched with an initial contribution from Thoratec.

Burnett's wife Deena reported that her husband had called her from the doomed plane to tell her that he and other passengers had become aware of the terrorist attacks on New York and Washington and that they were preparing to take action against those who had hijacked the flight. Grossman said that since the crash, the company "has received literally hundreds of calls from around the world asking how they might help Tom's family since hearing of his heroics in helping to divert United Airlines Flight 93 from its intended target." Grossman said Burnett's death "has been a great professional and personal loss for all of us at Thoratec. Tom made many significant contributions to our company and was a friend for many of us. He will be missed greatly."

Burnett is survived by his wife and three young daughters. Donations should be made payable to the Thomas E. Burnett Jr. Family Memorial Fund, c/o CIBC Oppenheimer Corp., Account #074-17387-10, 580 California Street, Suite 2300, San Francisco, CA 94104.

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