BBI Washington Editor
and DON LONG
BBI

WASHINGTON – Drug-eluting stent (DES) technology may no longer be the new kid on the block, but there is still plenty of updated information as use of the devices expands into other indications and more data is gathered on niche populations. Some of those niches include the use of stents with small vessels and complicated lesions, and in diabetic populations.

One of the most exciting studies presented on the opening day of the 16th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium were the results of the DIABETES trial. The trial was the first to specifically examine the use of stenting in the diabetic population. Prior research into diabetics and stents primarily has involved retrospective analysis of study data. Diabetes can alter the function of endothelial cells, smooth muscle cells and platelets, causing an overall arterial dysfunction that translates into more severe coronary artery disease and substantially increases the incidence of cardiovascular mortality. Studies also have shown that the rate of restenosis is greater in diabetic patients.

"Diabetics have been the bane of our existence in the cath lab," Gregg Stone, MD, director of cardiovascular research and education at the TCT-sponsoring Cardiovascular Research Foundation of Lenox Hill Hospital (New York), told conference participants during a presentation on the evolution of DES technology.

The objective of the DIABETES trial was to assess the efficacy of sirolimus-eluting stents following successful implantation in diabetic patients with de novo coronary stenoses. Both insulin- and non-insulin-dependent patients were included.

"I expected less benefit than what the study showed," Manel Sabaté, MD, of Hospital Clinico San Carlos (Madrid, Spain), principal investigator of the DIABETES trial, told Cardiovascular Device Update. "In my opinion, we knew there would be benefit, but I did not think that the real-world results would be as good. It was a pleasant surprise."

Four sites in Spain were included in the multicenter, prospective, randomized, placebo-controlled trial. There was no official sponsor of the trial, but the Spanish Society of Cardiology did provided a grant in 2003, and both the drug-coated and bare-metal stents used for comparison in the study were manufactured by the Cordis (Miami Lakes, Florida) division of Johnson & Johnson (J&J; New Brunswick, New Jersey).

The primary endpoint of the trial was in-stent late lumen loss as assessed by quantitative coronary angiography follow-up at nine months. The secondary endpoint was the rate of restenosis. A total of 160 patients were enrolled, half receiving bare-metal stents, and the other half receiving the sirolimus-eluting Cypher stents.

Trial results showed late lumen loss significantly reduced for patients in the sirolimus-eluting stents group compared to those with bare-metal stents. For restenosis, the sirolimus-eluting stent group was only 7.7% at nine-month follow-up, compared to 33% for patients treated with the bare-metal stent.

The rates of target lesion revascularization and major adverse cardiac events also were dramatically reduced in the sirolimus group at 7.5% and 11.3%, respectively, compared to 31.3% and 36.3% for those with bare-metal stents.

According to Sabaté, insulin-dependent patients treated with the sirolimus stent exhibited the same degree of reduction in restenosis compared to those treated with oral agents. Insulin-dependent patients are considered a harder patient subset to treat. He said the trial demonstrated that the use of the sirolimus-eluting stent in diabetics effectively reduced in-segment late-lumen loss and restenosis rate compared to the bare metal stent and the beneficial effect resulted in the significant reduction in the need for revascularization at the nine-month follow-up.

"The results are outstanding," Martin Leon, MD, president and CEO of the Cardiovascular Research Foundation, told CDU. "There were some early indications that these [stents] were not as effective in diabetic cohorts. But this showed a very dramatic result and really exceeded our expectations."

Leon said that this kind of study would only lead to increased confidence and expanded use of drug-eluting stent technology. "By the end of this year, the stent penetration rate in the U.S. is expected to be about 75%," Leon added. "This is an amazing shift over the past 18 months."

Patients with diabetes and multi-vessel disease have traditionally been classified as surgical candidates, he noted. But this data provides "a very strong sense" that clinicians are justified in using stents rather than surgery. Leon said that this research also paves the way for further examination of stenting with the diabetic population. A new 2,400-patient, unsponsored trial called FREEDOM – designed to compare the efficacy of surgery to drug-eluting stent intervention patients with diabetes – was scheduled to begin last month.

2-year TAXUS data show results sustained

Boston Scientific (Natick, Massachusetts) reported two-year follow-up data from its TAXUS IV clinical trial at the symposium, those results showing that the benefits reported at 12 months – for patients who received a paclitaxel-eluting stent compared to patients who received a bare-metal stent – were maintained at two years. The results support safety and efficacy, as demonstrated by low rates of target lesion revascularization (retreatment rate, or TLR) that were maintained at two years, the company said. The TAXUS group reported a 5.6% (36/645) TLR rate vs. a 17.5% rate (112/640) in the control group. The follow-up rate at two years was robust, with 97% of patients returning. The rate of patients living free of TLR events was 94.4% at two years for the TAXUS group vs. 82.6% for the control group.

Results for diabetic patients (including oral and insulin-requiring diabetics) in the TAXUS group also showed that benefits were maintained at two years. The TLR rate for diabetics was 8% (12/150) compared to 22% (35/159) in the control group. Diabetic patients – expected to represent roughly 40% of coronary interventions – are more likely than non-diabetic patients to experience restenosis following angioplasty and stenting with bare-metal stents and may stand to benefit substantially from drug-eluting stent technology, according to Boston Scientific.

"The TAXUS IV results at two years are exceptional and support the long-lasting safety and efficacy of paclitaxel-eluting stent technology," said Stone, principal investigator in the study. "These outcomes establish the durability of the Taxus stent in a broad range of complex patients and blockages, representing a true medical advance. At two-year follow-up, the incremental benefits of having received the Taxus stent system rather than a bare-metal stent continue to increase, with no evidence of late catch-up apparent."

Jim Tobin, president and CEO of Boston Scientific, said that this DES trial was the first "in which analysis of additional TLR events between one and two years shows a significant benefit for patients treated with the Taxus stent system. The data demonstrates a further increase of the overall TLR benefit compared to the control group."

TAXUS IV assessed the safety and efficacy of a paclitaxel-eluting DES in reducing restenosis in de novo lesions 10 mm to 28 mm in length and 2.5 mm to 3.75 mm in diameter. The study enrolled 1,326 patients at 73 sites in the U.S. The paclitaxel drug used in the Taxus stent is licensed from Angiotech Pharmaceuticals (Vancouver, British Columbia).

Boston Scientific also disclosed 30-day safety data from its TAXUS V clinical trial, which has been designed to assess the slow-release formulation of the Taxus Express2 paclitaxel-eluting stent system in 1,172 patients at 66 sites in the U.S. TAXUS V expands on the TAXUS IV pivotal trial by studying a higher-risk patient population, including patients with small vessels, large vessels and long lesions requiring multiple overlapping stents.

The TAXUS V trial – which includes the use of multiple stents as well as single stents – is designed to assess the safety and efficacy of a paclitaxel-eluting coronary stent in reducing restenosis in de novo lesions 10 mm to 46 mm in length and 2.25 mm to 4.0 mm in diameter. It has a primary endpoint of nine-month target vessel revascularization (TVR).

The results support early safety, as demonstrated by a low overall major adverse cardiac event (MACE) rate of 4.4% at 30 days, which is consistent with results from previous Taxus clinical trials. Thirty-day MACE was 3.7% in Group X and 5.1% in Group Y (the study remains blinded through the primary endpoint at nine months). The TVR rate was 0.7% in Group X and 1.2% in Group Y. Stent thromboses were also low, with a rate of 0.5% in Group X and 0.7% in Group Y.

Boston Scientific also reported data supporting safety from three post-market registries associated with the Taxus Express2. In total, these registries studied more than 7,000 patients at 236 sites around the globe. The company said the results were consistent with controlled Taxus studies. The ARRIVE peri-approval registry has enrolled nearly 2,600 consecutive patients at 50 sites in the U.S. (A peri-approval registry includes patients who are enrolled before and after a product is approved.) ARRIVE was initiated in cooperation with the FDA and is the first Taxus registry in the U.S.

Boston Sci said that results from ARRIVE demonstrated safety based on a site-reported 30-day adverse event rate of 2.7% (70/2,582), including site-reported cardiac death, myocardial infarction and reintervention of the target vessel. The registry reported a stent thrombosis rate of 1.3% (angiographically confirmed thrombotic events and all deaths less than 30 days without obvious cause). ARRIVE reported a 99% follow-up at 30 days. The company said that ARRIVE has demonstrated that consecutive enrollment yields a very diverse patient population involving patients receiving multi-vessel stenting (17%), left main stenting (3%), stenting of chronic total occlusions (2%), stenting of bifurcated lesions (8%), stenting of saphenous vein grafts (6%) and stenting of in-stent restenonic lesions (7%).

The Milestone II registry was designed as a follow-up to the Milestone I registry (which evaluated usage patterns of the Express2 bare-metal stent system) to assess the Taxus paclitaxel-eluting stent system. On a global basis, the registry has enrolled 3,688 patients at 164 centers in 32 countries.

The company unveiled six-month global data from MILESTONE II at TCT that it said supports safety and demonstrates that physicians are using the Taxus stent system to treat difficult lesions and cases, particularly in diabetic patients. MILESTONE II reported a 96% follow-up at six months.

Boston Scientific reported a 4.9% cardiac adverse event rate (CAE), a rate of 2.8% for repeat procedures and a 1.2% reported stent thrombosis rate per patient (angiographically confirmed thrombotic events and all deaths less than 30 days without obvious cause). For the overall diabetic population, which was 33.9% of the MILESTONE II patient population, the CAE rate was 6% and the need for repeat procedures was 3.6%. The WISDOM transitional registry was initiated in 2002 as part of a limited commercial launch of the Taxus stent system, to assess the usage patterns of the first Taxus slow-release formulation.

As an international, multi-center, prospective, observational registry, WISDOM is collecting and analyzing data on 778 patients in nine countries. The company unveiled one-year results for WISDOM that demonstrated safety based on site-reported clinical outcomes. The WISDOM database reports a 92% follow-up at 12 months with a population that is 33% diabetic. In the overall WISDOM patient population, the study reported a 5.2% CAE rate, a rate of 2% for reinterventions and a 0.6% reported stent thrombosis rate.

"Our TAXUS registries are providing invaluable 'real-world' data from nearly every corner of the globe and further demonstrate that the Taxus stent system is safe in the treatment of coronary artery disease," Tobin said. "These results are particularly impressive given the wide-range of patients, practices and clinical settings that were included in these studies."

Difficult-to-treat study backs Cypher

Results of a multi-center, prospective study involving two leading drug-eluting stents (DES) – the Cypher Sirolimus-eluting stent from Cordis and the Taxus Express 2 – were presented. The data indicated that patients with long areas of vessel blockage (more than 24 mm) treated with the Cypher DES had less in-stent late loss (tissue growth inside the stent) and less in-stent restenosis (reblockage) than patients treated with the Taxus DES or a bare-metal stent.

Both DES products "showed improvement over the bare metal stent in this difficult-to-treat patient population, with the Cypher stent showing better outcomes among the stents studied," said principal study investigator, Seung-Jung Park, MD, chief of interventional cardiology, ASAN Medical Center, a teaching affiliated hospital of Ulsan University (both Seoul, Korea).

Park noted that while prior studies of DES devices have included subsets of patients with long lesions, this is the first to focus exclusively on this hard-to-treat patient population. "Patients with very long lesions are among the most difficult to treat and [are] at higher risk for restenosis. These findings provide important new information for clinicians to consider when treating these types of patients," he said.

The presence of long lesions is only one factor that can place a patient at higher risk for restenosis, however. Other factors include narrow vessels, longer stent length and diabetes, since diabetic patients generally have more inflammatory responses to treatment for blocked vessels and a greater likelihood of cell regrowth proliferation that can lead to reblockage.

The study involved eight Korean centers, enrolling a total of 637 patients with long lesions – defined as lesions of at least 24 mm in length treated with stents 28 mm or longer. Patients were treated with the Cypher (n=294), Taxus (n=166) or bare metal stent (n=177) between February 2003 and February 2004, and they were followed for six months. The primary endpoint of the registry was six-month angiographic restenosis, determined via cardiac imaging. Secondary endpoints included late loss (vessel wall narrowing) and major adverse cardiac events (MACE), comprised of all-cause death, myocardial infarction (heart attack) and target lesions revascularization (TLR or retreatment).

The patient populations in the two arms of the study were matched at the baseline, including the percent of high-risk patients, such as diabetic patients: Cypher, 31% vs. Taxus, 31.9%; and overall stent length: Cypher, 42.8 mm vs. Taxus, 43.1 mm – though patients in the Cypher arm of the study had slightly narrower vessels (2.80 mm) vs. the Taxus arm (2.90 mm). Even with narrower vessels at the baseline, at follow-up, patients treated with the Cypher had 65% less in-stent late loss than patients treated with the Taxus (0.27 mm vs. 0.78 mm), and 65% less in-segment restenosis than patients treated with the Taxus (7.4% vs. 21.3%).

Additionally, Cypher-treated patients had a larger minimal in-stent diameter (vessel opening) than patients treated with the Taxus (2.45 mm vs. 1.98 mm, p<0.001), important for blood flow, and a lower average in-stent diameter stenosis (blockage) than those treated with the Taxus (10.4% vs. 29.3%, p<0.001) at late follow-up. Park concluded that the study's importance was in showing "how drug-eluting stents are performing over the long term with challenging patients, an important and growing patient population."

Founded in 1989, ASAN is the largest medical center in Korea. Its Cardiovascular Center performs about 2,500 percutaneous coronary interventions and publishes 20 articles annually.

AF treatment boosted by PLAATO

A novel heart implant device was successfully used in more than 200 patients with atrial fibrillation (AF), German researchers said. CardioVascular Center (Frankfurt, Germany) researchers were seeking to determine whether blocking one of the sources where blood clots are formed would prevent strokes from occurring in patients with AF. With the Percutaneous Left Atrial Appendage Transcatheter Occlusion (PLAATO) system, manufactured by ev3 (Plymouth, Minnesota), doctors use a catheter to place a blocking device at the opening of the left atrial appendage (LAA) inside the heart.

"In atrial fibrillation 90% of thrombi, or blood clots, form in the left atrial appendage which does not fulfill any physiological function," said Yves Bayard, MD, of the CardioVascular Center. "By blocking this appendage, we thought we might be able to artificially prevent strokes that are caused by clots."

The PLAATO System is CE-marked for treating LAA occlusion for occlusion but not cleared for U.S. marketing. AF can cause blood to pool inside the heart and form clots, leading to stroke, with estimated 15% of all strokes caused by AF. Warfarin anticoagulation therapy is standard for AF but comes with many contraindications.

Professor Horst Sievert said that PLAATO "may become a valuable alternative for patients with chronic, non-rheumatic [AF] in whom standard anticoagulation therapy is contraindicated or poorly tolerated." Of the more than 200 patients in whom Sievert and colleagues have performed LAA occlusion with the PLAATO device, only three have sustained a stroke thus far, and Sievert called this number "lower than we had originally anticipated. These results, while still early stage, give us great hope for the future of the PLAATO device in the treatment of atrial fibrillation."

PLAATO consists of a self-expanding cage covered with ePTFE (Gore-tex), delivered through a sheath designed for LAA access. It is retrievable before release and can be replaced with an alternate size to optimize sealing.

Kensey Nash takes PRIDE in TriActiv

In a report during a "Late-Breaking Trials" session, final results of the PRotection during saphenous vein graft Intervention to prevent Distal Embolization (PRIDE) clinical trial – examining the safety and effectiveness of Kensey Nash's (Exton, Pennsylvania) TriActiv System to support FDA approval, were reported. PRIDE randomized the TriActiv System against other approved embolic protection systems or the standard of care, measuring major adverse cardiac event (MACE) rates in treating saphenous vein graft (SVG) disease. PRIDE enrolled 894 patients at 68 U.S. sites and 10 European sites. The non-inferiority portion of the trial, which compared the TriActiv System to approved devices, enrolled 631 patients and generated the data presented at TCT.

TriActiv is a distal protection system used during SVG interventions to minimize complications. PRIDE "achieved its objective of showing non-inferiority of the TriActiv System to approved devices, as measured by the primary endpoint of 30-day MACE rates, demonstrating that the system had equivalent clinical outcomes to two previously approved embolic protection systems," Kensey Nash said. Designed to prevent debris, dislodged during stent procedures, from embolizing downstream and causing coronary events such as heart attack, TriActive has three key system features: an embolic protection balloon, and an active flush and extraction system, combined, to remove problematic debris. The company says that TriActiv is the only such system "that actively removes the debris from the vessel by gently flushing the treatment area within the vessel."

Joseph Carrozza, MD, chief of the section of interventional cardiology at Beth Israel Deaconess Medical Center (Boston) and principal investigator of PRIDE, presented the final data which showed a 10.2% (32/313) MACE rate for procedure-related events for the TriActiv compared to 10.1% (32/318) for the active control group, which represented the approved devices for this indication – the GuardWire from Medtronic (Minneapolis) and the FilterWire from Boston Scientific. Primary endpoint of MACE at 30 days was 11.2% for the TriActiv arm of the study, 10.1% for the control arm. Complication rates often run as high as 20% in vein graft procedures performed without embolic protection, Kensey Nash said.

Carrozza said, in summary: "I was especially interested to note the system's apparent advantage in preventing the most severe MACE, those with CK-MB level rises above eight times normal levels ... [W]e consider it to be a next-generation embolic protection system." Kensey Nash submitted an application for 510(k) FDA clearance of the system, to treat SVG, in July. It is CE-marked in Europe. Joseph Kaufmann, president and CEO of Kensey Nash, said that system launch in the U.S. will come immediately after FDA clearance.

An estimated 550,000 coronary artery bypass surgeries are performed worldwide as treatment for coronary artery disease, and current sales for embolic protection systems used during SVG procedures are put at $100 million worldwide, with growth to be driven substantially by next-generation products and expanded indications.

CryoPlasty a potential option

Suffers of critical limb ischemia have a hopeful new alternative to below-the-knee amputation with the minimally invasive CryoPlasty procedure from CryoVascular Systems (Los Gatos, California), according to research presented at TCT. Outcomes of the first patients to receive the therapy showed that 95% of the patients were able to avoid "almost certain" below-the-knee amputation as a result of treatment with the PolarCath System Infrapopliteal Catheter, using the CryoPlasty technique to gently cool and revascularize atherosclerotic arteries.

PolarCath treats clogged arteries by cooling them to -10 degrees C/+14 degrees F with a balloon filled with liquid nitrous oxide. Cooling of the plaque and artery wall results in three potential benefits: weakening of the plaque to promote universal dilation and less vessel trauma, reduction of vessel wall recoil, and inducing of apoptosis (cell death in the smooth muscle cells implicated in restenosis). These effects appear to minimize some of the complications that contribute to the reclogging of the vessels, according to the researchers.

Critical limb ischemia is the later stage of peripheral arterial disease (PAD), also known as peripheral vascular disease, or clogged arteries in the arms and particularly the legs. Patients with critical limb ischemia are at risk for ulceration, infection, gangrene or amputation. About 160,000 amputations are performed annually in the U.S. as a result, according to The Sage Group (Atlanta), an independent research firm.

James Joye, DO, director of the cardiac catheterization lab at El Camino Hospital (Mountain View, California) and co-inventor of the CryoPlasty technique, noted the lack of treatment options for those with this type of advanced disease – many of them diabetic. "The CryoPlasty procedure is a conservative 'no harm' therapy that can be employed early in the disease process and can be repeated if necessary without hindering future treatment options. It may be possible to delay progression of the disease to the limb-threatening stage."

In the study, 26 lesions in arteries below the knee were treated in 20 patients who had leg pain at rest or ischemic ulceration and gangrene, with all 20 receiving the CryoPlasty technique using the PolarCath System as the primary therapy and six with severely blocked vessels undergoing atherectomy to create a channel that would allow passage of the catheter. Limb salvage with freedom from major amputation was achieved in 19 patients (95%), with only one requiring follow-on below-the-knee amputation; five (25%) underwent toe or transmetatarsal amputation of pre-existing gangrene; one was treated for bilateral disease underwent subsequent bypass surgery in one limb.

"Once it is established that lifestyle changes and drug therapy aren't working for these people, the CryoPlasty technique is a reasonable first-line interventional option, even before standard angioplasty," Joye said. "It appears to avoid some of the potential complications that occur in traditional angioplasty, such as dissection and restenosis."

The FDA in February cleared the PolarCath System Infrapopliteal Catheter for treatment of atherosclerotic lesions in the infrapopliteal and tibioperoneal arteries (below the knee). The procedure is available at about 100 hospitals and will be available at around 600 hospitals across the country by the end of this year, CryoVascular Systems said.

No long-term gains in vascular brachytherapy

Vascular brachytherapy, generally used to prevent short-term complications in angioplasty patients, provides no benefit five years post-treatment. That is the primary conclusion of new research presented at TCT. The Cardiovascular Research Foundation's Leon called the results of the study "sobering." He added: "What we had once viewed as a powerful therapy to prevent short-term tissue overgrowth [restenosis] actually may not have any lasting benefits."

Vascular brachytherapy is a radiation therapy involving the use of localized gamma- or beta-radiation administered through a catheter. This radiation technique has been shown to limit overgrowth of vascular tissue in these patients. Leon and colleagues conducted a five-year follow-up study from the Gamma-One Trial, a randomized blinded placebo-controlled clinical trial that originally showed a reduction of in-stent restenosis by 40% to 50% in the first six months for patients receiving radiation. However, what the study revealed is that in each subsequent year of the follow-up, there was deterioration in the radiation's effect. After five years, in-stent restenosis in the placebo group and radiation group were equivalent.

The findings would appear to be bad news for Novoste (Norcross, Georgia), which is the leader in vascular brachytherapy (VBT) to prevent restenosis. Its flagship product is the Beta-Cath system, designed to utilize radiation to stave off the frequent reclogging after angioplasty or angioplasty and stent placement. The company saw sagging sales and a lack of enthusiasm for its technology with the pre-approval preoccupation with drug-eluting stent (DES) technology and then even worse results following DES approvals in the U.S. in 2003 and earlier this year and that technology's clear benefits in reduced levels of restenosis. VBT also has the disadvantage of requiring a fairly large infrastructure as compared to stent placement.

In an attempt to shore up its VBT sales, the company earlier this year signed an agreement with Guidant (Indianapolis) to facilitate a transition to Novoste products by existing customers of Guidant's VBT system in the U.S. and Canada. Guidant discontinued its VBT business in the U.S. and Canada – specifically sales of its Galileo Intravascular Radiotherapy System. Novoste paid $2.5 million to Guidant at the signing of the transaction and agreed to pay a 5% royalty on its net sales of all vascular brachytherapy products in the U.S. and Canada, up to an additional payment of $4 million.

In discussing the VBT study results, Leon said, "For the first time, we have documented in a randomized controlled study that vascular brachytherapy exhibits a delayed catch-up over several years. By the time five years had past, the patients we studied were no better off than if they had received no radiation treatment at all." Gamma-One compared the angiographic and clinical outcomes in 252 patients randomized to either vascular brachytherapy with iridium-192 radiation or placebo for in-stent restenosis lesions. Compared to placebo, patients treated with radiation experienced a three-fold higher frequency of late target lesion revascularization, most of which occurred between six months and three years.

Leon warned that his research might have broader implications. "This study serves as a warning that optimism surrounding short-term outcomes does not always guarantee sustained long-term results, reinforcing the need for longer-term follow-up in clinical research," he said.

Other reports cite treatment gains

As shown in another TCT report, direct intra-renal drug delivery using the Benephit Infusion System, made by FlowMedica (Fremont, California), can increase the beneficial effects of the drug enoldopam on the kidneys while minimizing side effects in patients undergoing coronary procedures, according to a new clinical study.

Hooman Madyoon, MD, presented data from a physician-sponsored study of the Benephit system, conducted at St. Joseph's Medical Center (Stockton, California) and ScrippsClinic (La Jolla, California) under Paul Teirstein, MD. The trial evaluated the Benephit system for its ability to deliver fenoldopam directly to the renal arteries, thereby preventing certain changes in kidney physiology associated with radiocontrast nephropathy (RCN) – a common cause of acute kidney failure among patients undergoing interventional and diagnostic cardiovascular procedures. Although fenoldopam can increase blood flow to the kidneys and improve kidney function, its systemic use to prevent RCN is limited since high doses are associated with significant lowering of blood pressure.

Fenoldopam delivered intra-renally via the Benephit Infusion System significantly improved kidney function, according to investigators. In contrast, the intravenous administration of fenoldopam at the same dose improved kidney function only minimally. At the same time, systemic drug levels were significantly less following intra-renal delivery of fenoldopam vs. intravenous treatment. Correspondingly, blood pressure reduction was significantly less following intra-renal delivery. In addition, the beneficial effects on kidney function lasted at least two hours following intra-renal treatment, according to preliminary results.

The FlowMedica Benephit Infusion System consists of a Bifurcated Infusion Catheter and a unique Introducer Sheath. It received 510(k) clearance by the FDA in January for the infusion of physician-specified agents to the renal arteries.

At an industry breakfast, Biotronik (Berlin) highlighted its clinical development of the absorbable metal stent (AMS). "We have set a goal of becoming the largest European player in vascular intervention with our absorbable metal stent technology," said Marlou Janssen, director of sales and marketing at Biotronik. AMS has just entered clinical study phase, and Janssen said that Biotronik is the only company currently in trials with this technology. First human implants of the absorbable stent were performed at St. Blasius Hospital (Dendemonde, Belgium) and at Imelda Hospital (Bonheiden, Belgium). This first human experience involved the implant in January of absorbable stents in 20 patients with critical limb ischemia and diagnosed with below-the-knee atherosclerotic disease.

One-month data on the first eight patients was presented in February. All arteries showed perfect patency at one month with no sign of renarrowing, and initial stent absorption was evident. At three months, a success rate of 100% in-limb recovery and a patency rate of 89% were reported. The six-month data were reported in September, with one amputation, a 78.9% rate of patency and a complete absorption of the stent within the expected timeframe. Biotronik said that this success led it to implant the stents in patients with coronary artery disease. The first patients were implanted July 30, to begin the PROGRESS-AMI trial.

Preliminary data from the first five patients was presented at the industry breakfast. After four weeks there were no major coronary events, the primary endpoints of the study. Two patients were free of angina, two had minor angina, and one was readmitted for atypical chest pain. There was about 50% absorption of the stent in all patients after three weeks. Researchers intend to finish the 65-patient study in the next few months, and larger studies in Europe and the U.S. will begin in 2005, Biotronik said.

John Crew, MD, presented the next generation of the SuperStitch vessel closure device from Sutura (Fountain Valley, California) at a symposium on vascular closure. Sutura's new device is designed on the "as simple as 1-2-3 concept," he said, making it easier for physicians to deploy the SuperStitch which closes the femoral puncture site using the catheter sheath introducer to access the femoral artery wound, the company said.

Anthony Nobles, president and CEO of Sutura, said that the 1-2-3 design "provides physicians the security of suture and the simplicity that's easier than a plug." The SuperStitch devices allow physicians to close the femoral puncture site using the catheter sheath introducer to access the femoral artery wound. Sutura has received FDA 510(k) clearance for its F8 and F6 SuperStitch devices as well as the CE mark. Sutura also has met all of the registration requirements for selling the SuperStitch devices in Australia.

Sutura develops minimally invasive vessel closure devices to suture the puncture created in the femoral artery during catheter-based procedures, primarily in the fields of cardiology and radiology.

Stephen Ramee, MD, co-principal investigator of the MAVErIC Clinical Trial, presented positive preliminary 30-day data from the MAVErIC II trial and one-year data from the MAVErIC I trial. The MAVErIC studies, comprising 498 patients, are designed to evaluate the short- and long-term safety and efficacy of the Exponent Carotid Stent System and the GuardWire Balloon Occlusion device from Medtronic (Minneapolis) in reducing the incidence of stroke and death in patients with carotid artery disease.

"The preliminary data from these studies suggests that the GuardWire system, when used with the Exponent carotid stent, is successful in treating high-risk patients with carotid artery disease," Ramee said. "This data indicates that balloon occlusion devices, such as the GuardWire system, used in this manner are similar to filter devices and can produce favorable results in carotid stenting procedures. Depending on the patient, it may be appropriate to fully seal a vessel via a balloon system to prevent stroke and this data suggests that the GuardWire system is a viable option for meeting this important objective."

The MAVErIC II trial preliminary 30-day results showed a major adverse event (MAE) rate of 5.3%. MAE includes any stroke, myocardial infarction (MI) and/or death. The MAE rate for MAVErIC II included an MI rate of 2%, a death rate of 1% and stroke rate of 3.3%. The study also assessed lesion, device and procedural success, with both the Exponent stent and GuardWire system performing well in the study. The MAVErIC II trial completed enrollment in August 2003 and is being performed at 34 centers in the U.S. Patients in the MAVErIC II trial will be followed up to one year after their procedure. Medtronic anticipates that final patient follow-up will occur this fall.

The MAVErIC I clinical trial was a 99-patient feasibility study designed to demonstrate the safety of the Self-Expanding Exponent Carotid Stent with the GuardWire Temporary Occlusion and Aspiration System for the treatment of carotid stenosis. At one year, the study found an MAE rate of 5.1%, which was unchanged from the 30-day results. The study also demonstrated positive device, lesion and procedural success. The MAVErIC I study completed enrollment in December 2002 and was performed at 16 U.S. centers.

Medtronic said it intends to conduct the MAVErIC III Clinical Trial in the U.S., beginning this fall, to study the safety and efficacy of the Exponent Carotid Stent System with the Interceptor PLUS Filter System in reducing the incidence of stroke and death in patients with carotid artery disease.

EndoTex Interventional Systems (Cupertino, California) reported preliminary 30-day results of the CABERNET trial, a study designed to evaluate the safety and efficacy of carotid artery stenting (CAS) as a minimally invasive alternative for treating carotid artery disease. The presentation was by L. Nelson Hopkins, MD, principal investigator, professor and chairman of neurosurgery at Buffalo State University (Buffalo, New York). CABERNET – a multi-center registry that enrolled a total of 488 symptomatic and asymptomatic patients at 15 U.S. and four international sites – examines the use of EndoTex's NexStent Carotid Stent and Boston Scientific's FilterWire EX and EZ Embolic Protection Systems for treating patients who are at high-risk for carotid endarterectomy (CEA), the surgical treatment for carotid artery disease.

"We are encouraged by the 30-day results of the CABERNET trial to demonstrate the safety and efficacy of the NexStent Carotid Stent and Boston Scientific FilterWire EX and EZ as a minimally invasive system to treat carotid artery disease," said Joseph Tartaglia, president and CEO of EndoTex. "We are confident that the performance of this unique and novel system will be reinforced as we continue to collect results for our one-year endpoint." Matthew Jenusaitis, president of Boston Scientific's Peripheral Interventions business, said, "[Our] involvement with EndoTex continues to be an extremely successful collaboration. The combination of both companies' technologies potentially provides a greater variety of innovative treatment options for patients with carotid artery disease."

"It is exciting to see that with the release of each of the subsequent carotid stenting trial results, the outcomes appear to demonstrate continued improvement," said Hopkins. "The results from CABERNET suggest that CAS in this high-risk patient subset appears competitive with the major CEA trials."

In patients enrolled in the study, the 30-day composite major adverse event (MAE) rate, defined as all-cause stroke, death and myocardial infarction (MI) – was 3.8%. This corresponds to a per-patient breakdown of MAE events to include death, 0.5%; stroke, 3.4% and MI, 0.2%. The NexStent device success, defined as successful delivery and placement of the stent at the intended target site, was 96.9%. The device success for the FilterWire EX and EZ, defined as successful placement within the target vessel, was 99.1%. One-year primary endpoint CABERNET results will be available in mid-to-late 2005.

The NexStent delivery system used in the CABERNET trial was a 5 Fr, over-the-wire delivery system. This low-profile system can deliver a stent capable of covering a 9mm reference vessel diameter. The FilterWire EZ System is a low-profile embolic filter mounted on a 0.014" guide wire that is delivered through a monorail exchange delivery catheter. It is Boston Scientific's first-generation embolic protection product and was used in both the CABERNET and BEACH carotid trials. It also is the first filter-based system cleared for treatment of saphenous vein graphs in the U.S.

Possis Medical (Minneapolis) reported full results from its 480-patient, post-marketing AngioJet Rheolytic Thrombectomy In Patients Undergoing Primary Angioplasty for Acute Myocardial Infarction trial (AiMI). The study was configured as a multicenter, prospective randomized two-arm trial comparing AngioJet Rheolytic Thrombectomy (RT) followed by definitive treatment (angioplasty, stent and eptifibatide) vs. immediate definitive treatment only, in patients undergoing intervention for acute myocardial infarction, or heart attack.

While RT is approved for use in thrombotic coronary lesions, the results of the study do not support its routine use with primary coronary intervention (PCI) in all ST-segment elevation MI (STEMI), or heart attack, patients, the company said. As measured by nuclear scan, the 197 intent-to-treat patients in the AngioJet arm had a mean final infarct size of 12.5%, while the 205 patients in the control arm had a mean final infarct size of 9.8%. The percentage of infarct size refers to the percentage of myocardial tissue that remains non-viable after the heart attack and the assigned treatment. The p-value for this difference was 0.0182. For all of the secondary endpoints, there was no statistically significant difference between the two treatment arms. The study was not powered for clinical endpoints.

Investigators noted that the randomization procedure might have introduced some selection bias against enrolling high-risk patients with large thrombus. In addition, there was a statistically significant difference in baseline flow favoring the control arm in the trial.

The study was not large enough to identify sub-groups that might have benefited from RT, with statistical precision, they said. For example, the AiMI investigators noted that the possible benefit of RT in STEMI patients with large thrombus burdens could not be assessed from this study. The company and its investigators plan further studies to evaluate the clinical value of RT in patients with STEMI and thrombotic lesions.

The study used the AngioJet XMI catheter, which is FDA-approved for removing thrombus in native coronary arteries and in saphenous vein bypass grafts. The primary endpoint of the study was final infarct size at one month, as measured by SPECT imaging. The study was carried out at 32 sites in the U.S. and Canada. Arshad Ali, MD, FACC, of the Guthrie Clinic Sayre (Sayre, Pennsylvania), served as principal investigator of the AiMI Study and presented the results.