2008

ASE Issues New Standards for Carotid Ultrasound
February 5, 2008—The American Society of Echocardiography (ASE) issued a new consensus statement by James H. Stein, MD, et al for interpreting and responding to results of a carotid ultrasound study for cardiovascular disease risk assessment (J Am Soc Echocardiogr. 2008;21:93-111). This consensus statement, which was endorsed by the Society for Vascular Medicine, is available at the ASE-sponsored Web site, www.seemyheart.org. The statement provides specific guidance for detecting early atherosclerotic plaques and increased carotid intima-media thickness (CIMT). By following the consensus statement, doctors will be more confident recommending aggressive preventive therapies if ultrasound reveals the walls of the carotid arteries are thicker than established cut points for patients of similar age, gender, and race. Identifying patients who have hidden risks for heart disease without invasive procedures should help improve patient care and treatment success rates. The ASE noted that carotid ultrasound has been used as a research tool for more than 2 decades and is increasingly turning into an established clinical practice. To guide doctors on when it should be used and what the results mean, the consensus statement provides standards for patient selection, scanning technique, imaging protocol and interpretation. In addition, it provides recommendations for training and certification of sonographers and readers.

According to Dr. Stein, ASE is not recommending routine use of the procedure for all patients, despite the proven value of ultrasound scans for arteries. The guidelines are designed to alert physicians to the types of patients for whom the test may be useful. Carotid ultrasound to measure wall thickness and detect early plaques is most useful when other clinical information puts patients on the borderline between needing aggressive therapy and following a more standard approach, stated Dr. Stein.

• Patients that may benefit from this test include those who do not already have heart or arterial disease; and
• Are clinically determined to be at "intermediate" risk for a heart attack or cardiac death in the next 10 years;
• Have a family history of premature cardiovascular disease in a close relative;
• Have significant abnormalities in one or more known cardiovascular risk factors (such as young patients with genetic cholesterol disorders or who are heavy smokers); or
• Are women younger than 60 with at least two cardiovascular risk factors.

This test can be considered if the level of aggressiveness of therapy is uncertain and additional information about the burden of early vascular disease or future cardiovascular disease risk is needed. Imaging should not be performed unless the results would be expected to alter therapy. The guidelines set the 75th percentile as the threshold for aggressive treatment. Patients who have CIMT greater than that level for patients of similar age, gender, and race are considered to be at increased cardiovascular risk. Also, patients with carotid plaques are considered at increased risk. The consensus panel recommended a comprehensive scan of all segments of both carotid arteries to look for the presence of plaques, as well as imaging of the far walls of each common carotid artery so CIMT can be measured. The presence of carotid plaque or increased CIMT is a marker of increased risk of heart attack, stroke, or death from cardiovascular disease.

2007

US Task Force Does Not Recommend Screening for Asymptomatic Carotid Disease
December 18, 2007—The US Preventive Services Task Force (USPSTF) recommendation for clinical guidelines for the screening for carotid artery stenosis (CAS) has been published in Annals of Internal Medicine (2007;147:854-859). The USPSTF issued a grade D recommendation that stated, "Do not screen for asymptomatic CAS in the general adult population." This is an update of the task force's 1996 statement about screening for asymptomatic CAS in the general population. The task force examined the evidence on the natural history of CAS, systematic reviews of the accuracy of screening tests, observational studies of the harms of screening and treatment of asymptomatic CAS, and randomized, controlled trials of the benefits of treatment for CAS with carotid endarterectomy.

The USPSTF stated that it makes recommendations about preventive care services for patients without recognized signs or symptoms of the target condition. It bases its recommendations on a systematic review of the evidence of the benefits and harms and an assessment of the net benefit of the service. The USPSTF stated that it recognizes that clinical or policy decisions involve more considerations than this body of evidence alone. Clinicians and policymakers, the task force said, should understand the evidence but individualize decision making to the specific patient or situation. The recommendation and background information are also available on the US Agency for Healthcare Research and Quality's USPSTF Web site, www.ahrq.gov/clinic/prevenix.htm.

Boston Scientific's 3-Year CABERNET and BEACH Results Presented at TCT
October 23, 2007—Boston Scientific Corporation (Natick, MA) announced 3-year results from its carotid artery stenting clinical trials, CABERNET (Carotid Artery Revascularization Using the Boston Scientific FilterWire EX/EZ and the EndoTex NexStent) and BEACH (Boston Scientific EPI: A Carotid Stenting Trial for High Risk Surgical Patients). The studies evaluated the effectiveness of stenting with embolic protection for patients at high risk for carotid endarterectomy (CEA). Co-Principal Investigator L. Nelson Hopkins, MD, presented the 3-year CABERNET and BEACH results at the 19th annual Transcatheter Cardiovascular Therapeutics scientific symposium in Washington, DC. The CABERNET clinical trial was designed to evaluate the safety and efficacy of Boston Scientific's NexStent carotid stent and FilterWire EZ embolic protection system. The BEACH clinical trial was designed to evaluate the safety and efficacy of the carotid Wallstent Monorail endoprosthesis and FilterWire EZ embolic protection system. CABERNET and BEACH were both prospective, nonrandomized, single-arm clinical trials enrolling 454 patients and 480 patients, respectively, who were at high risk for CEA, the company stated.

Dr. Hopkins reported that the CABERNET major stroke rate was 1.3% at 30 days and 2.8% at 3 years. The 3-year CABERNET data showed that the ipsilateral stroke rate was 2.9% at 30 days and 4.9% at 3 years. In the BEACH trial, the major stroke rate was 1.7% at 30 days and 8.1% at 3 years, and the ipsilateral stroke rate was 3.1% at 30 days and 7.7% at 3 years. The NexStent is FDA approved to treat carotid artery disease in patients who are at high risk for CEA. The Wallstent is currently under review by the FDA and is available for investigational use only, the company advised.

CAS Comparable to AHA Guidelines for CEA in Abbott Vascular's Studies
October 23, 2007—Abbott Vascular (Redwood City, CA) announced that two carotid stenting trials examining outcomes in real-world patients demonstrated for the first time results that are comparable to guidelines for patients treated with carotid artery endarterectomy (CEA) published by the American Heart Association (AHA) in Circulation (1998;97:501-509). William Gray, MD, presented the results of these studies at the 19th annual Transcatheter Cardiovascular Therapeutics scientific symposium in Washington, DC.

According to the company, patients treated with carotid stents were studied in Abbott's CAPTURE 2 (Carotid Acculink/Accunet Postapproval Trial to Uncover Rare Events) and EXACT (Emboshield and Xact Postapproval Carotid Stent Trial) postmarketing trials. These trials enrolled 4,111 patients. The 30-day patient outcome results were comparable to the AHA outcome guidelines for patients <80 years of age who undergo CEA. The guidelines recommend stroke and death rates that are within 3% for asymptomatic patients and 6% for symptomatic patients. The CAPTURE 2 study included 1,987 patients and utilized Abbott's Acculink carotid stent system and Accunet embolic protection system. The EXACT study included 2,124 patients and utilized Abbott's Xact rapid-exchange carotid stent system and Emboshield BareWire rapid-exchange embolic protection system. In both trials, the key objective was to determine if carotid stenting could be performed safely in a real-world clinical setting by physicians with varying levels of experience. The primary endpoints were death, stroke, and myocardial infarction at 30 days. The demographics of patients in both trials were similar. Patient enrollment for the CAPTURE 2 trial is ongoing. The EXACT trial is closed, and 30-day follow-up has been completed, the company stated.

Dr. Gray reported the 30-day composite endpoints of stroke and death. The combined stroke and death rates in asymptomatic patients <80 years of age were 3.1% in CAPTURE 2 and 3% in EXACT; the rates in symptomatic patients <80 years of age were 6% and 7.3%, respectively; and, for the combined populations, the rates were 3.8% and 4%, respectively, within 30 days of treatment.

"With these two very large, well-conducted, real-world carotid artery stenting trials, not only has carotid stenting achieved a comparable outcome to guidelines established for patients who undergo carotid surgery, but it also did so in a population of patients who are at high risk for experiencing adverse events from surgery," commented Dr. Gray. "This is significant because this is the first time physicians have achieved results in high-surgical-risk candidates that are comparable to the long-standing guidelines that were established for lower-surgical-risk candidates, demonstrating that stenting can provide a reliable nonsurgical alternative for patients facing the difficult decision of how to manage their carotid artery disease."

Study Shows Potential Benefits of Staged Approach to CAS and Cardiac Surgery
October 30, 2007—Early and long-term results from a study of staged carotid angioplasty and stenting (CAS) followed by cardiac surgery in patients with severe asymptomatic carotid artery stenosis were published by Jan Van der Heyden, et al in Circulation (2007;116:2036-2042).

According to the investigators, the strategy for treating patients with severe asymptomatic carotid artery stenosis and cardiac disease remains unresolved. Staged or combined carotid endarterectomy in these patients offers the potential benefit of decreased neurological morbidity during and after cardiac surgery; however, in high-risk patients with severe coronary artery disease, chronic obstructive pulmonary disease, or renal impairment, the incidence of death and stroke is significantly higher.

Therefore, the investigators commenced a prospective, single-center study designed to evaluate the feasibility and safety of CAS before cardiac surgery in neurologically asymptomatic patients. They analyzed the periprocedural and long-term outcomes of 356 consecutive patients who underwent CAS before cardiac surgery. The procedural success rate of CAS was 97.7%. The death and stroke rate from time of CAS to 30 days after cardiac surgery was 4.8% (n=17). The myocardial infarction rate from time of CAS to 30 days after cardiac surgery was 2% (n=7), and the combined death, stroke, and myocardial infarction rate was 6.7% (n=24). Distal embolic protection devices were used in 40% of the cases, the investigators reported.

The investigators concluded that this large cohort of asymptomatic patients who underwent staged CAS and cardiac surgery experienced a low periprocedural complication rate. The high rate of freedom from death and stroke during the 5 years of follow-up supports the long-term durability of this approach. These findings suggest that this new strategy may become a valuable alternative in the treatment of patients with combined carotid and cardiac disease, stated the investigators in Circulation.

Lumen Biomedical's FiberNet and Xtract Receive CE Mark
September 26, 2007—Lumen Biomedical, Inc. (Plymouth, MN) announced that the FiberNet Embolic Protection System (EPS) and the Xtract Aspiration Catheter have received CE Mark. According to the company, the FiberNet EPS is indicated for use during percutaneous interventional procedures in carotid arteries. The device captures debris as small as 40 µm within a 3D array of fibers. The filter is then removed through the single-lumen design of the Xtract aspiration catheter supplied with the system. The FiberNet EPS requires no delivery system. The filter is mounted on a .014-inch steerable guidewire with a crossing profile ranging from 2.3 mm to 2.9 mm. A ≥1.5-cm landing zone allows more flexibility for filter placement. The three approved fiber-based filters conform to vessels of 3.5 mm to 7 mm. The full model range (vessels 1.75 mm to 7 mm) is included in ongoing US clinical trials: EPIC US feasibility study (Evaluating the Use of the FiberNet Emboli Protection Device in Carotid Artery Stenting) and the RETRIEVE study (Evaluating the Use of the FiberNet Embolic Protection System in Saphenous Vein Grafts).

According to the company, the Xtract aspiration catheter is indicated for removal of fresh, soft emboli or thrombi in coronary and carotid vessels. The Xtract catheter features a braided shaft for responsive delivery and kink resistance with a soft, curved tip to negotiate obstructions and provide directional suction. It is available in 4.2-F, 5-F, and 5.8-F sizes. The large, single-lumen design of the Xtract catheter provides constant and powerful aspiration during the procedure. The Xtract catheter has also received FDA clearance for similar use in the arterial system, the company stated.

Invatec's ARMOUR Study of the Mo.Ma System With CAS Approved by FDA
August 3, 2007—Invatec (Roncadelle, Brescia, Italy) announced that it received FDA approval to conduct the ARMOUR (Proximal Protection with the Mo.Ma Device During Carotid Stenting) clinical study of the company's Mo.Ma proximal protection device used in combination with FDA-approved carotid stents. The study will enroll 228 patients who are at highly increased risk of complications during carotid endarterectomy. Patients will be enrolled at 20 sites in the US and Europe. ARMOUR's Co-Principal Investigators are Gary M. Ansel, MD, of Riverside Methodist Hospital in Columbus, Ohio; and L. Nelson Hopkins, MD, of the University of Buffalo in Buffalo, New York.

According to the company, Mo.Ma is a proximal flow blockage cerebral protection device that allows interventionists to establish the use of embolic protection during carotid stenting before lesion crossing. The device utilizes the principle of carotid flow cessation by endovascular clamping via common carotid artery and external carotid artery balloon occlusion. Mo.Ma functions like a guiding catheter with high stability and back-up support given by the two integrated distal balloons. Mo.Ma is available in 9-F and 8-F sizes, featuring 6-F and 5-F inner lumens, respectively. The ARMOUR study will use a 9-F Mo.Ma device with 6-F carotid stents. The ARMOUR study is intended to allow for the company's future studies and device approvals in the US. Since its introduction in Europe in 2001, the device has been evaluated in multiple clinical studies showing device safety, efficacy, and broad applicability in standard and complex cases, the company stated.

Stenosis After CAS Studied
June 1, 2007—A study by G.J. de Bortst, et al in the European Journal of Vascular & Endovascular Surgery evaluated the long-term effect of carotid angioplasty and stenting (CAS) of the internal carotid artery (ICA) on the ipsilateral external carotid artery (ECA) and concluded that significant progression of ≥50% stenosis in the ECA occurs after CAS (2007;33:657-663). The study also found that there was greater progression of disease in the ipsilateral compared with the contralateral ECA and that progression of disease in the ECA did not lead to the occurrence of occlusion during follow-up. In the study, the investigators prospectively registered the pre- and postinterventional duplex scans obtained from 312 patients (mean age, 70 years) who underwent CAS. Duplex scans were scheduled the day before CAS, 3 and 12 months after the procedure, and annually thereafter, to study progression of obstructive disease in the ipsilateral ECA compared to the contralateral ECA. The duplex ultrasound criteria used to identify ECA stenosis ≥50% were peak systolic velocities of ≥125 cm/s. Preprocedural evaluation of the ipsilateral ECA demonstrated ≥50% stenosis in 32.7% of cases versus 30% contralateral. Three (1%) ipsilateral and contralateral ECA occlusions were noted. After stenting, five (1.8%) occlusions were seen vs 1% contralateral. No additional ipsilateral occlusions and two additional contralateral occlusions were noted at extended follow-up. The prevalence of ≥50% stenosis of the ipsilateral ECA (Kaplan-Meier estimates) progressed from 49.1% at 3 months, to 56.4%, 64.7%, 78.2%, 72.3%, and 74% at 12, 24, 36, 48, and 60 months, respectively. Contralateral prevalences were 31.3%, 37.7%, 41.7%, 43.1%, 46.0%, and 47.2%, respectively (P<.001). Progression of stenosis was more pronounced in 234 patients (75%) with overstenting of the carotid bifurcation (P=.0004).

Cordis Launches Aviator Plus for Carotid and Renal PTA
June 7, 2007—Cordis Corporation, a Johnson & Johnson company (Miami, FL), announced the worldwide launch of the Cordis Aviator Plus balloon dilatation catheter for use in percutaneous transluminal angioplasty procedures for patients with carotid and/or renal artery blockages. The announcement was made at the 61st Annual Meeting of the Society for Vascular Surgery in Baltimore, Maryland.

According to the company, the Aviator Plus combines a high-pressure expansion and low-profile, .014-inch rapid-exchange or single-operator system that facilitates fast inflation and deflation times to limit the period of distal ischemia. The low profile may reduce the risk of plaque disruption and embolization when crossing the lesion. The Aviator Plus features a <.9-mm manicured tip, a 3.3-F shaft, and modified Duralyn balloon material on a 4-F system. Duralyn allows for precise and consistent inflation diameters. The device is available in 4-mm to 7-mm diameters and 1.5-cm to 4-cm lengths on 142-cm shafts, Cordis stated.

Boston Scientific Commences SONOMA Study of NexStent
May 31, 2007—Boston Scientific Corporation (Natick, MA) announced enrollment of the first patient in the SONOMA postmarket approval study of the NexStent carotid stent system used in conjunction with the FilterWire EZ embolic protection system. Subbarao Myla, MD, is Principal Investigator. SONOMA, a multicenter US surveillance registry that will include a minimum of 1,500 patients at 100 sites, aims to confirm the safety and efficacy of the NexStent and FilterWire EZ in routine clinical practice. The devices were approved in 2006 for use in high-risk patients, based on the 454-patient CABERNET trial results. Patients enrolled in SONOMA are scheduled for follow-up at 30 days and 12 months after stent implantation. An independent core lab will analyze the duplex ultrasound evaluation of a 500-patient cohort.

Kensey Nash's ProGuard Gets CE Mark for Carotid Use
April 10, 2007—Kensey Nash Corporation (Exton, PA) announced that it has received CE Mark approval to expand the indication for the third generation of its embolic protection technology, the TriActiv ProGuard system, for use in the carotid anatomy. The company launched the device in Europe last year for use in saphenous vein graft procedures. To support the CE Mark, Kensey Nash completed a pilot trial to study the safety of the TriActiv ProGuard device in carotid patients at five sites in the US and Europe. The data showed no incidence of major strokes or death in the 50-patient study. Kensey Nash is also currently enrolling patients in the PROGUARD carotid pivotal study, a 300- to 400-patient registry intended to support FDA clearance, the company stated.

According to Kensey Nash, the TriActiv ProGuard system is the company's newest version of the TriActiv system product line, which incorporates "LFX" (Local Flush and eXtraction) technology designed for use in branched anatomy, such as those of the carotid arteries. The system incorporates a balloon protection guidewire, a flush catheter, and an automated extraction system to remove debris. The TriActiv ProGuard system has been clinically studied and can be used in combination with any approved carotid stent in the marketplace, the company stated.

ev3's Onyx HD 500 Liquid Embolic System Receives HDE to Treat Cerebral Aneurysms
April 16, 2007—ev3 Inc. (Plymouth, MN) announces that it has received an FDA Humanitarian Device Exemption (HDE) approval for the Onyx HD 500 liquid embolic system for the treatment of intracranial aneurysms. The HDE allows ev3 to market the Onyx for use in patients with wide-necked cerebral aneurysms. The HDE is limited to saccular, sidewall aneurysms with dome-to-neck ratios of <2 mm that are not amenable to treatment with surgical clipping. In July 2005, the Onyx 18 and 24 systems received FDA approval for the treatment of cerebral arteriovenous malformations.

According to the company, marketing of the Onyx HD 500 will be preceded by a lengthy period of education and training of a small group of leading neurovascular specialists. Once trained, this group of proctors will help ensure that the use of Onyx HD 500 is carefully controlled as is required for all HDE-approved devices. A US Investigational Device Exemption study and two European clinical studies examined approximately 200 patients with wide-necked aneurysms who were effectively treated with the Onyx HD 500. Wide-necked aneurysms occur in approximately 20% of the 17,000 patients who are treated with embolic coils each year in the US, the company stated.

CMS Does Not Expand CAS Coverage
April 30, 2007—The Centers for Medicare & Medicaid Services (CMS) announced that it has elected not to implement the changes in covered indications for percutaneous transluminal angioplasty (PTA) of the carotid artery concurrent with stenting (CAS) that were outlined in the proposed decision memorandum of February 1, 2007, with the exception of clarifications regarding the use of embolic protection devices and the facility certification and recertification process. This decision only changes coverage criteria in section B4 of the Medicare National Coverage Determination (NCD) Manual for CAS (20.7). The NCD language can be found in Appendix B of the decision memorandum, which is available on the CMS Web site at www.cms.hhs.gov.

CMS stated that coverage for PTA with CAS remains available for patients who are at high risk for carotid endarterectomy (CEA) who also have symptomatic carotid artery stenosis ≥70% when procedures are performed using FDA-approved CAS systems and embolic protection devices; patients who are at high risk for CEA and have symptomatic carotid artery stenosis between 50% and 70%, only when the procedure is part of an FDA-approved clinical trial or postapproval study; and patients who are at high risk for CEA and have asymptomatic carotid artery stenosis ≥80%, only when the procedure is part of an FDA-approved clinical trial or postapproval study.

Other limitations are that CAS is covered only when used with an embolic protection device and is, therefore, not covered if deployment of the distal embolic protection device is not technically possible; the five facility-certification requirements are also unchanged. CMS modified the process for completing facility certification and recertification in the NCD Manual. This modification includes specific data submission requirements for facility recertification as well as a timeline for this process; CAS for patients who are not at high risk for CEA remains covered only in FDA-approved clinical trials or under the clinical trial policy.

In considering whether the evidence was sufficient to conclude that PTA with CAS for patients with symptomatic stenosis ≥50 who are at high risk for CEA improves health outcomes, CMS reviewed the registry data from the CAPTURE, ARCHeR, CASES-PMS, and CREATE studies, the SAPPHIRE trial, and the EVA-3S and SPACE randomized trials. The agency stated that although the majority of comments favored expansion of coverage to the 50% to 69% group based on results from CAPTURE, ARCHeR, and CASES, CMS concluded that the evidence from the EVA-3S and SPACE randomized trials was more compelling and did not support expansion. CMS also noted that, since the posting of the proposed decision, the Blue Cross and Blue Shield Association Technical Evaluation Center (TEC) completed another review of CAS. The TEC concluded that CAS did not meet the TEC criteria to assess whether a technology improves health outcomes, the same conclusion reached in its 2005 review. According to the TEC, the perioperative morbidity and mortality rate should be <6% for CAS to be considered an alternative to CEA and improve health outcomes.

CMS has determined that the language that requires a surgeon credentialed to perform CEA to determine whether patients are at high risk for CEA was overly restrictive and has removed this language from the final decision, but it stressed the importance of ensuring appropriate patient selection. CMS explained that its 2005 opinion included this requirement based largely on the SAPPHIRE trial, in which "each center was required to assemble a multidisciplinary team of physicians comprising a neurologist, either a vascular surgeon or a neurosurgeon, and an interventional physician," and "patients were randomly assigned to a procedure only if all members of the team were in agreement that the patient was a suitable candidate for either endarterectomy or stenting."

CMS noted that, as evident from the public comments, this issue has created a serious "turf" war between various physicians who treat carotid artery disease. CMS said it encourages physicians of different specialties to work together to determine the best course of treatment for patients. CMS continues to strongly encourage consultation with a surgeon qualified to perform CEA and consideration of establishing a multidisciplinary team including a surgeon qualified to perform CEA to the evaluation of patients prior to performing carotid PTA and CAS.

Abbott's EXACT and CAPTURE 2 30-Day Results Presented at ACC
March 26, 2007—Abbott Vascular (Redwood City, CA) announced that 30-day results from two of the company's studies confirm that carotid stenting can be performed with positive results by physicians with a variety of background experience in real-world settings in patients who are not favorable candidates for surgery. William A. Gray, MD, presented interim results from the first 1,500 patients enrolled in EXACT (Emboshield and Xact Post Approval Carotid Stent Trial) and from the first 600 patients enrolled in CAPTURE 2 (Carotid Acculink/Accunet Postapproval Trial to Uncover Rare Events), at the 56th Annual American College of Cardiology Scientific Session in New Orleans.

The primary endpoint of death, stroke, and heart attack at 30 days was 4.6% in EXACT and 5.2% in CAPTURE 2. Results from EXACT and CAPTURE 2 also demonstrated a low rate of 30-day major stroke and/or death in patients treated with Abbott's carotid stent systems (1.8% in EXACT, 1.3% in CAPTURE 2). The EXACT postapproval study utilizes Abbott's Xact rapid-exchange carotid stent system and Emboshield BareWire rapid exchange embolic protection system. CAPTURE 2 utilizes Abbott's Acculink carotid stent system and Accunet embolic protection system. Clinical evidence from these studies is being used to support Abbott's request to the CMS to reconsider its carotid stenting coverage policy. Last month, CMS proposed expanding carotid stenting coverage to asymptomatic high-surgical-risk Medicare patients with carotid stenosis of >80%.

According to Abbott, the use of these systems has only been studied in limited clinical trials before FDA approval in the pivotal SECuRITY (Registry Study to Evaluate the Neuroshield Bare Wire Cerebral Protection System and X-Act Stent in Patients at High Risk for Carotid Endarterectomy, 2004) study. In the EXACT study, 4.5% of patients experienced periprocedural complications, compared to 7.5% in the SECuRITY study, the company stated.

"The results from these two studies reaffirm that carotid stenting is a safe, effective, minimally invasive treatment option for patients with carotid artery disease who may be at risk of experiencing adverse events from surgery," commented Dr. Gray. "The results also suggest that patient outcomes are improving over time as the practice of carotid stenting increases."

CASES-PMS Study Shows CAS Is Safe and Effective for High-Risk Patients
March 2, 2007—The Society of Interventional Radiology (SIR) announced that preliminary 1-year data from CASES-PMS add to the growing body of evidence that carotid stenting with embolic protection is safe and effective for patients at the highest risk for adverse events and substantiates the low adverse event rates reported previously in the SAPPHIRE trial. CASES-PMS is a multicenter, prospective, single-arm trial of 1,493 patients at 73 sites. Barry T. Katzen, MD, presented the study at the SIR's 32nd Annual Scientific Meeting held March 1-6, 2007, in Seattle, Washington.

The SIR noted that the CASES-PMS trial was designed to assess the safety and efficacy outcomes of carotid artery stenting using the Precise nitinol stent and Angioguard emboli capture guidewire (Cordis Corporation, a Johnson & Johnson company, Miami, FL) when performed by physicians with varied experience in carotid artery stenting utilizing a formal training program. The study demonstrated that using a detailed training program in carotid artery stenting for physicians with various levels of experience produced outcomes that were similar to those of the highly experienced physicians who participated in the SAPPHIRE trial.

According to the SIR, the CASES-PMS trial compares the outcomes of patients in the CASES-PMS trial to those of the SAPPHIRE trial stent cohort and confirms the long-term results and safety profile of carotid stenting with embolic protection in patients who are high risk for surgery or whose surgery failed (the population for whom the treatment is currently approved). The primary endpoints of the study measured the 30-day major adverse event rate (MAE)—death, stroke, and heart attack—which were likely to be procedure-related events, and the 1-year MAE, which included the 30-day rate plus death and same-side stroke from 31 days to 1 year. The preliminary 1-year cumulative MAE of 11.9% in the CASES-PMS trial is similar to the 12.2% rates seen with the SAPPHIRE trial stent cohort and lower than the 20.1% for the surgical arm of the SAPPHIRE trial. The CASES-PMS overall stroke rate at 1 year was 4.8% (7% in symptomatic patients and 4.2% in asymptomatic).

"Patients with severely blocked carotid arteries are at high risk for stroke, but many patients with vascular disease are not good candidates for surgery," commented Dr. Katzen. "Now we know we can safely offer these high-risk patients carotid stenting, saving many people from future strokes."

Dr. Katzen further stated, "We are excited to see a similar safety profile for physicians who were involved in the training program at 73 different sites. This is an excellent model to introduce a new technique very safely into the mainstream and will allow us to train more physicians, enabling more patients to have this important treatment to prevent stroke."

FDA Approves Cordis's Precise Rapid-Exchange CAS System
February 15, 2007—Cordis Corporation (a Johnson & Johnson company, Miami, FL) announced FDA approval to market the Precise RX nitinol self-expanding stent and Angioguard RX emboli capture guidewire system to treat carotid artery stenosis. The Precise RX and Angioguard RX are different from Cordis's over-the-wire carotid system approved last year. The RX, or rapid exchange, version facilitates single operator use and more efficient manipulation of the catheter and guidewire during stenting procedures. Approval of the new Cordis carotid system was announced at the Arizona Heart Institute's International Congress XX on Endovascular Interventions held in Scottsdale, Arizona on February 9-15, 2007.

Cordis also announced the initiation of SAPPHIRE Worldwide, a 10,000-patient global registry to assess the 30-day rate of major adverse events (death, stroke, or myocardial infarction) following the placement of a stent in high-surgical-risk patients with carotid artery disease. The stent procedure includes use of an emboli distal protection system. The registry will include up to 275 centers with low, medium, and high annual carotid stent implant volumes, from both academic and private hospitals.

"It's great to get the same devices on the rapid exchange delivery system," commented Anil Chhabra, MD, who performed the first carotid case with the Precise RX and Angioguard RX systems. "The Angioguard RX emboli capture guidewire system was very easy to advance through a very tight lesion, and the auto tapering of the Precise RX nitinol self-expanding stent was apparent in the excellent wall apposition across the different-sized internal and common carotid arteries."

CMS Proposes Changes to Coverage Policy for Carotid Artery Stenting
February 1, 2007—The Centers for Medicare & Medicaid Services (CMS) announced a proposal to change its coverage policy for carotid artery stenting (CAS). The proposed National Coverage Determination (NCD), which includes a coverage expansion that reflects the latest evidence on the effective use of stenting, is posted on the CMS Web site, www.cms.hhs.gov/mcd/viewdraftdecisionmemo.asp?id=194. The February 1 posting of this proposed decision memorandum marks the beginning of a 30-day public comment period, ending on March 3. Interested parties who wish to submit comments should visit the tracking sheet for this analysis at www.cms.hhs.gov/mcd/viewtrackingsheet.asp?id=194.

The proposed changes to the NCD are:

• Restrict the current coverage for patients who are at high risk for carotid endarterectomy (CEA) and have symptomatic carotid artery stenosis ≥70% to patients <80 years of age.
• Restrict coverage for symptomatic patients who are ≥80 years only to those with ≥70% stenosis in accordance with the Category B IDE clinical trials regulation (42 CFR 405.201), the clinical trial policy (Medicare NCD Manual 310.1), or the NCD on CAS postapproval studies (Medicare NCD Manual 20.7B3)
• Expand coverage to patients who are at high risk for CEA and have asymptomatic carotid artery stenosis ≥80% and who are <80 years of age.
• Establish that the surgeon performing the surgical consultation that determines a patient's high-risk status must be properly credentialed to perform CEA as determined by the facility.

The CMS clarifications to the current NCD are:

• CAS is only covered when used with an embolic protection device and is, therefore, not covered if deployment of the distal embolic protection device is not technically possible.
• The five facility certification requirements are unchanged, but CMS proposes to modify the process for completing the certification and recertification process in the NCD manual.

CMS proposes to maintain current CAS coverage as follows:

• Patients at high risk for CEA who have symptomatic carotid artery stenosis between 50% and 70% in accordance with the Category B IDE clinical trials regulation (42 CFR 405.201), the clinical trial policy (Medicare NCD Manual 310.1), or the NCD on CAS postapproval studies (Medicare NCD Manual 20.7B3).
• Patients who are ≥80 years of age with asymptomatic stenosis ≥80% in accordance with the Category B IDE clinical trials regulation (42 CFR 405.201), the clinical trial policy (Medicare NCD Manual 310.1), or the NCD on CAS postapproval studies (Medicare NCD Manual 20.7B3).
• CAS for patients who are not at high risk for CEA in the opinion of a surgeon credentialed to perform CEA remains covered only in FDA-approved Category B IDE clinical trials under 42 CFR 405.201 or under the clinical trial policy.

CMS stated that this proposed decision only changes coverage criteria in section B4 of the Medicare NCD Manual for CAS (20.7). Coverage as determined in the other sections of 20.7 will continue without modification. The proposed NCD language can be found in Section IX of the decision memorandum. CMS is requesting public comments on the proposed determination. After considering the public comments and any additional evidence, CMS will issue a final decision memorandum by May 2, 2007.

On September 1, 2004, following FDA approval of the Acculink carotid stent system and the Accunet embolic protection system (Guidant Endovascular Solutions, which was then part of the former Guidant Corporation, Indianapolis, IN), CMS announced its intention to expand coverage of CAS beyond procedures conducted with a Category B IDE in an FDA preapproval clinical trial. Coverage was expanded to CAS with an FDA-approved device for participants in a large FDA-mandated postapproval study conducted by Guidant.

On December 17, 2004, CMS proposed expanded coverage of CAS for patients at high risk for CEA. The proposed Medicare coverage was restricted to high-risk patients with symptomatic narrowing of the carotid artery of ≥70% and to asymptomatic high-risk patients enrolled in prospective clinical studies. The expanded coverage became effective on March 17, 2005.

On August 2, 2006, CMS reviewed and accepted reconsideration requests submitted on March 31, 2006 by Guidant and on June 14, 2006, by Abbott Vascular (Redwood City, CA). Abbott manufactures and markets the Xact carotid stent system and the Emboshield BareWire RX embolic protection system, which received FDA approval on September 15, 2005. Abbott also now manufactures and markets the Acculink carotid stent system and the Accunet embolic protection system, which were acquired as part of Guidant's Endovascular Solutions business unit in April 2006.

Guidant and Abbott requested CMS to provide coverage of CAS for the treatment of carotid artery disease in high-surgical-risk patients who are symptomatic with >50% stenosis or asymptomatic with >80% stenosis and determined by the treating physician to require carotid revascularization, which is in line with the FDA indication. Also, CMS was requested to remove the language in the current policy stating that the patient must be a poor candidate for CEA "in the opinion of a surgeon."

The recent proposal has fallen short of the requested changes and has prompted varying reactions from the interventional community. While some interventionists believe the proposed reimbursements do not go far enough—and should be coextensive with the FDA indication—the expansion of coverage to the asymptomatic population is generally welcome.

Interventional cardiologist William A. Gray, MD, Director of Endovascular Services at NY Presbyterian Hospital/Columbia University Medical Center in New York City commented on the effect that coverage of asymptomatic patients <80 years of age will have on treatment: "Patients at high surgical risk will now have greater access to this FDA-approved technology. It will also obviate the need to enroll them into postmarket registries in order to allow for their care, which will decrease the overall cost of care since it cost both the sponsoring company and participating hospital to administer these registries."

Frank Criado, MD, Chief of Vascular Surgery and Director of the Center for Vascular Intervention at Union Memorial Hospital in Baltimore, added that the effect on patient treatment will be significant: "The current standard of care in the US 'dictates' treatment of patients with critical, >80%, asymptomatic carotid stenoses. A good number of such patients, particularly those at high anatomic or medical risk for CEA, may be excellent candidates for CAS. And we should, of course, include those who wish to avoid an operation and have percutaneous stenting instead."

A controversial CMS proposal is the maintenance of the requirement that a vascular surgeon make the determination that the patient is high risk for CEA. Interventional radiologist Barry T. Katzen, MD, Director of the Baptist Cardiac & Vascular Institute in Miami, commented on this requirement: "I don't think a surgical consultation should be required. The fact is that there are very specific definitions of which patients are high risk for surgery that have been defined by the clinical trials. They include clinical criteria and anatomic criteria. To interpose any physician who says they don't agree, or that a patient is not high risk just because they are willing to do it, is not appropriate. If there are definitions that define what is high risk, which is defined by Medicare according to the trials, I'm not sure what the role of a surgical consultation is. I think the patient should be offered both."

Dr. Gray concurred: "This surgical consultation requirement is without precedent in cardiovascular medicine. To establish the primacy of one specialty over another where there is overlap in expertise by edict is problematic, to say the least, from a variety of perspectives, most of which are obvious."

Dr. Gray ruminated on what this latest proposed coverage means for the future of carotid artery stenting in the US: "This coverage expansion is best viewed in the larger perspective of CAS as a fully diffused therapy and technology over the next several years, assuming good results from the normal-risk trials. When that day comes, it will be important that there be no gaps in CMS coverage where it is appropriate for the Ôreasonable and necessary' aspects of patient care, which is CMS's charge. This coverage decision helps to fill in the significant gap that existed in the high-surgical-risk asymptomatic population but there is still work to do in the majority of patients in this country with carotid artery disease in gaining access to CAS for them."

Asked if the proposed coverage decisions were too restrictive, Dr. Criado thought they were not: "Treating all-comers with CAS would be uncalled for at this time. Such strategy cannot be supported by available evidence. The only acceptable exception relates to patient enrollment in a well-controlled, FDA-approved clinical trial. CEA remains the standard of care at present."

Dr. Katzen agreed that the decision reflects the current state of knowledge: "I think this is an incremental step that is important in the acceptance of carotid stenting moving forward."

ev3's Protégé RX Carotid Stent Approved by FDA
January 24, 2007—ev3 Inc. (Plymouth, MN) announced FDA approval of the Protégé RX carotid stent, which, when used in conjunction with ev3's SpideRX embolic protection device, is indicated for the treatment of carotid artery disease in patients who are at high risk for adverse events from carotid artery surgery. The FDA cleared the SpideRX for carotid use in February 2006. According to the company, the FDA approval was supported by the CREATE (Carotid Revascularization with ev3 Inc. Arterial Technology Evolution) Trial demonstrating the safety and efficacy of the Protégé RX stent and the SpideRX device when used together to treat carotid artery disease patients at risk for stroke and also at high risk for adverse events from surgery. The CREATE Trial enrolled 419 patients in 31 centers in a prospective, nonrandomized study. The results of the CREATE trial compared favorably with performance criteria that were based on the results of previous carotid stenting trials, the company stated.

The Protégé RX is available in both straight and tapered stent configurations providing a variety of device options to address the broad range of patient anatomy present in carotid artery disease. The rapid-exchange platform allows for a single physician to operate the device as compared to over-the-wire designs that require multiple operators. The SpideRX distal filter embolic protection system permits physicians to use their guidewire of choice and is cleared by the FDA for use in both carotid arteries and saphenous vein grafts. The Protégé RX and the SpideRX devices, which are sold separately, are also commercially available in Canada, Europe, and several countries in Latin America and Asia, the company noted.

"The Protégé RX carotid stent has an innovative delivery system that allows physicians to place the stent accurately and also provides great visible confirmation due to its distinct radiopaque markers," commented Gary Ansel, MD, national Co-Principal Investigator for the CREATE trial. "The SpideRX embolic protection device is unique because it allows physicians to use any guidewire they choose to cross the lesion just as they would in any other endovascular intervention."

2006

CAPTURE: CAS Is Safe and Effective by Broad Base of Trained Interventionists
December 14, 2006–The CAPTURE (Carotid Acculink/Accunet Post-Approval Trial to Uncover Unanticipated or Rare Events) study results have been published online by Catheterization and Cardiovascular Interventions: the Journal of the Society for Angiography and Interventions (SCAI), with print publication expected in an upcoming issue of the journal.

CAPTURE studied the Rx Acculink carotid stent and the Rx Accunet filter from Abbott Vascular (Redwood City, CA), which were approved by the FDA in 2004 for the treatment of patients with severe carotid atherosclerosis who were at high risk for carotid endarterectomy.

The report by William A. Gray, MD, et al for the CAPTURE Trial Collaborators examines outcomes of carotid stenting postapproval of the devices and after diffusion of the technology to a broad cross-section of physicians and hospitals. By contrast, the investigators noted that before this study, the pivotal study data examining carotid stenting with embolic protection as a less-invasive alternative to endarterectomy for high-surgical-risk patients have been acquired under controlled conditions with highly selected physicians and hospitals.

According to the investigators, CAPTURE is a prospective, multicenter registry to assess the safety of carotid stenting by physicians with varying levels of experience as a measure of the adequacy of physician training, and to identify rare and unexpected device-related complications. The primary endpoint was a composite of death, any stroke, or myocardial infarction within 30 days postprocedure. In the study, 353 physicians enrolled 3,500 patients at 144 sites. The results, as detailed in Catheterization and Cardiovascular Interventions, showed that the 30-day primary endpoint event rate was 6.3% (95% CI: 5.5% to 7.1%) and did not differ significantly among the three operator-experience levels (5.3%, 6%, and 7.4%; P=.31) from most to least experienced, respectively. There were no differences in outcomes among physician specialties when adjusted for case mix, and there were no unanticipated device-related adverse events. The investigators concluded that the CAPTURE results compare favorably to those achieved in the predicate pivotal investigations and the results suggest that the postapproval transfer of this new therapy to the community practice setting via carotid stent training programs is effective in preparing physicians with varying experience levels and specialty training backgrounds.

According to SCAI, CAPTURE was designed with patients undergoing a neurological examination before the stenting procedure, at 24 hours after the procedure, and at 30 days. The physicians who examined patients for complications were independent of those who performed the stenting procedure, an aspect which is one of the study's major strengths because it ensures confidence that the data are robust, meaningful, and applicable in community practices, said Christopher J. White, MD, Editor-in-Chief of Catheterization and Cardiovascular Interventions. SCAI said that carotid stenting experts hope such data will persuade CMS to expand coverage for carotid stenting. Medicare coverage is currently available only for patients who are at high risk for surgery and have symptoms before the procedure, but not those who are symptom-free despite severely narrowed carotid arteries. CMS is now re-evaluating that policy in light of the new data from CAPTURE and other postmarket surveillance studies, the SCAI stated.

"The ability to transfer the technology to the community was successful," commented Dr. Gray. "The study involved multiple physician specialties, multiple experience levels, and multiple sites with very broad geographic representation, and demonstrated that, regardless of these differences, outcomes were similar across the board." Dr. White added, "The CAPTURE trial is a giant step toward achieving the goal of proving that, in the foreseeable future, nonsurgical carotid stent placement will replace surgery as the treatment of choice for stroke prevention."

Kensey Nash Begins Carotid Trial of TriActiv ProGuard
November 14, 2006–Kensey Nash Corporation (Exton, PA) announced that it has commenced enrollment of PROGUARD, a 300- to 400-patient pivotal study for its TriActiv ProGuard embolic protection system in carotid stenting procedures. Gary S. Roubin, MD, PhD, and Rajesh Dave, MD, will serve as Co-Principal Investigators for the study, which will take place at up to 35 US sites and five European sites. If successful, the PROGUARD trial will support a 510(k) submission, currently anticipated in early 2008 following the expected completion of enrollment, the company stated.

According to the company, the TriActiv ProGuard system incorporates Local Flush and eXtraction (LFX) technology designed for use in branched arteries. The system incorporates three features designed to reduce the incidence of embolic stroke during carotid stenting procedures: a balloon protection guidewire, a flush catheter, and an automated extraction system to remove debris. The system has been studied and can be used in combination with any approved stent on the market. Earlier this year, Kensey Nash completed a pilot trial to study the safety of the TriActiv ProGuard device in carotid patients at five sites in the US and Europe. The data showed no incidence of major strokes or death in the 50-patient study. The company said that the data are supporting a CE Mark application, which is currently pending.

Boston Scientific Announces BEACH Results and FDA Approval of NexStent
October 23, 2006–Boston Scientific Corporation (Natick, MA) announced 2-year data from its BEACH carotid artery stenting (CAS) clinical trial, which evaluates the effectiveness of stenting with embolic protection for patients who are at high risk for carotid endarterectomy (CEA). The results were presented at the 18th annual Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium in Washington, DC. The BEACH trial was designed to evaluate the company's carotid Wallstent monorail endoprosthesis and the FilterWire EX and, later, the FilterWire EZ embolic protection systems. BEACH is a prospective, nonrandomized, single-arm clinical trial that enrolled 480 patients in the pivotal phase of the trial. These patients were considered at risk for surgery due to anatomical or comorbid factors.

According to the company, BEACH's 2-year results continue to evaluate long-term safety and efficacy. The ipsilateral stroke rate steadily declined from 3.1% at 0 to 30 days, to 2.3% at 31 days to 1 year, and to .9% between 1 and 2 years. The BEACH study also demonstrated declining death rates from 7.5% through 1 year to 6.1% between 1 and 2 years. In addition, long-term efficacy was evaluated with ultrasound data indicating a continued reduction in mean maximum peak systolic velocity. The progressive reduction in velocity from 346 cm/s before the stenting procedure to 130 cm/s out to 2 years postprocedure suggests no progressive restenosis from 6 months to 2 years, the company stated.

"Surgery was not an attractive option for these patients who are at increased risk for stroke," commented Christopher White, MD, Co-Principal Investigator of the BEACH study. "These results are encouraging because they suggest Boston Scientific's carotid artery stenting system may not only minimize the risk of stroke after the procedure, but may be a durable treatment with the incidence of stroke declining over time."

In related news, Boston Scientific announced on November 3 that the FDA has approved the NexStent carotid stent and Monorail delivery system for use in patients with carotid artery disease who are at high risk for surgery. The NexStent is manufactured by EndoTex Interventional Systems, Inc. (Cupertino, CA) and has been distributed exclusively by Boston Scientific outside the US since receiving CE Mark approval in 2005. Boston Scientific said it will acquire EndoTex within 90 days under the terms of the companies' existing agreements. Boston Scientific's FilterWire EZ embolic protection system, which was studied with the NexStent in the CABERNET clinical trial, is still pending FDA 510(k) clearance, the company stated.

According to the company, the NexStent carotid stent is a laser-cut, nitinol stent with a rolled sheet design that enables one stent size to adapt to multiple diameters in tapered or nontapered vessel configurations. The device's self-sizing feature is designed to provide adaptability when treating lesions in the carotid arteries, and its closed-cell configuration is designed to increase lesion coverage and provide a smooth inner lumen to help facilitate delivery and retrieval of ancillary devices.

EVA-3S Trial Results in NEJM Compare CEA and CAS
October 19, 2006–In the New England Journal of Medicine (2006;355:1660-1671), Jean-Louis Mas, MD, et al, writing for the Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) Investigators, published the results of a multicenter, randomized, noninferiority trial to compare carotid artery stenting (CAS) with endarterectomy (CEA) in patients with a symptomatic carotid stenosis of at least 60%. The primary endpoint was the incidence of any stroke or death within 30 days after treatment. According to the investigators, the trial was stopped prematurely after the inclusion of 527 patients for reasons of both safety and futility. The 30-day incidence of any stroke or death was 3.9% after CEA [95% Confidence Interval (CI), 2 to 7.2] and 9.6% after CAS (95% CI, 6.4 to 14); the relative risk of any stroke or death after CAS as compared with CEA was 2.5 (95% CI, 1.2 to 5.1). The 30-day incidence of disabling stroke or death was 1.5% after CEA (95% CI, 0.5 to 4.2) and 3.4% after CAS (95% CI, 1.7 to 6.7); the relative risk was 2.2 (95% CI, 0.7 to 7.2). At 6 months, the incidence of any stroke or death was 6.1% after CEA and 11.7% after CAS (P=.02). There were more major local complications after CAS and more systemic complications (mainly pulmonary) after CEA, but the differences were not significant. Cranial nerve injury was more common after CEA than after CAS. The investigators concluded that in this study of patients with symptomatic carotid stenosis of 60% or more, the rates of death and stroke at 1 and 6 months were lower with CEA than with CAS.

In an accompanying commentary in the New England Journal of Medicine (2006;355:1726-1729), "Carotid-Artery Stenting–Case Open or Closed?" Anthony J. Furlan, MD, reviewed the EVA-3S trial results and contrasted them to the findings of the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE), the Stent-Supported Percutaneous Angioplasty of the Carotid Artery versus Endarterectomy (SPACE), and the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) trials.

According to Dr. Furlan, certain differential factors among the studies include whether there was symptomatic or asymptomatic stenosis, the use of embolic protection devices, the incidence of periprocedural stroke, and the "learning curve" for CAS, which Dr. Mas, et al, also discussed. As Dr. Furlan noted, the data reported in the EVA-3S may be significantly different from other trial results because in the EVA-3S trial, interventionists used five different stents and seven different cerebral protection devices, and experience with only two procedures was required for any new device used. By comparison, the ongoing CREST study, funded by the National Institutes of Health, enrolled 1,472 patients for a lead-in phase that required a training program of up to 20 implantations per investigator using a single type of stent and cerebral protection system.

Dr. Furlan stated, "Although the EVA-3S trial raises concerns about the safety of carotid stenting and bolsters the call for standardized training and credentialing requirements, it cannot be considered the final word on carotid stenting for patients with an average surgical risk."

"Given the evidence to date, and assuming a complication rate of less than 6% for stenting, the only widely accepted indication for carotid artery stenting remains its use in symptomatic patients who have stenosis of the internal carotid artery exceeding 70% and who also have a high surgical risk," concluded Dr. Furlan. "All other patients should be treated medically, undergoing carotid endarterectomy if indicated, or should be placed in a clinical trial."

Conor Medsystems Announces EuroSTAR 2-Year Data
September 5, 2006–Conor Medsystems, Inc. (Menlo Park, CA) announced 2-year follow-up clinical data from the first arm of its pivotal EuroSTAR study of single- and multivessel coronary artery disease. Keith D. Dawkins, MD, presented the clinical results at the European Society of Cardiology/World Congress of Cardiology 2006 in Barcelona, Spain. According to the company, 176 lesions were treated in 145 patients using the CoStar stent formulated to release a therapeutic dose of 10 µg of paclitaxel per 17-mm stent over approximately 30 days (based on in vitro measurements). At 24-month follow-up, the target lesion revascularization rate was 3.6%, compared to 2.8% at 12-month follow-up, and the cumulative major adverse cardiac event rate at 24 months was 10.4%, compared to 8.3% at 12-month follow-up. There were no reported cases of stent thrombosis between the cessation of antiplatelet therapy at 6-month and 24-month follow-up.

The company stated that its stents have been specifically designed for vascular drug delivery, in contrast to conventional surface-coated stents. The CoStar stent incorporates hundreds of small holes, each acting as a reservoir into which drug-polymer compositions can be loaded. In addition, the CoStar stent uses bioresorbable polymers that are absorbed by the body after the drug is released. The company advised that the CoStar stent is not available for sale in the US where it is an investigational device.

Gore Begins Enrollment for EMPiRE Study, Acquires NIT
July 27, 2006—Gore & Associates (Flagstaff, AZ) announced that site initiation and enrollment has begun in the EMPiRE (Embolic Protection with flow Reversal) Clinical Study. According to the company, this investigational clinical study is designed to demonstrate the safety and efficacy of the Gore Neuro Protection System when used for embolic protection during carotid artery stenting procedures. The first patients were enrolled and successfully treated for narrowing of the carotid arteries at the University of Buffalo. All of the patients recovered from their procedures without incident, and have been discharged from the hospital, the company stated.

According to the company, the Gore Neuro Protection System is a unique embolic protection system developed by Juan Parodi, MD. The system operates by reversing the flow of blood at the treatment site. Flow reversal enables physicians to perform carotid interventions confident that liberated emboli will be safely directed away from the brain. Flow reversal is achieved by selectively occluding the common carotid and external carotid arteries' blood flow. By establishing the shunt between the carotid artery and femoral vein, blood from the opposite side of the brain is redirected via the circle of Willis and collateral vessels to the lower-pressure venous return. Embolic particles are captured in a filter outside the body.

"The Gore Neuro Protection System is an important advancement in protecting patients during carotid artery stenting procedures," commented L. Nelson Hopkins, MD, Chairman of Neurosurgery at the University of Buffalo and Co-Principal Investigator for the EMPiRE study. "The system eliminates the need for physicians to cross lesions unprotected and the associated risks of emboli going to the brain and causing a stroke. We believe it will allow us to treat a broader group of patients with greater confidence."

In related company news, on July 7, Gore announced that it has acquired Neural Intervention Technologies, Inc. (NIT, Ann Arbor, MI), a medical device company that is developing a novel liquid embolic material for the treatment of blood vessel defects. Financial details and other terms of the agreement were not disclosed. According to Gore, NIT was founded in 2003 based on the Algel technology developed by biomedical engineers Timothy Becker, PhD, and Daryl Kipke, PhD, and licensed from the University of Michigan and AzTE, a technology transfer company for Arizona State University. Algel is an alginate-based embolic material designed to fill blood vessel defects thereby displacing blood pressure effects and preventing vessel rupture. The material is delivered by microcatheters using a controlled delivery system for the treatment of vascular diseases such as cerebral arteriovenous malformations and aneurysms. With the acquisition of NIT, Gore stated that it will commence a phase 1 trial of the alginate liquid embolic targeting presurgical embolization of arteriovenous malformations.

Lumen Initiates FiberNet Carotid Trial, Receives FDA Clearance for Xtract Catheter
July 17, 2006—Lumen Biomedical, Inc. (Plymouth, MN) announced the initiation of its EPIC (Evaluating the Use of the FiberNet Embolic Protection Device In Carotid Artery Stenting) IDE Feasibility Study in the US. The company stated that Gary M. Ansel, MD, has successfully treated the first three US patients with the FiberNet system during carotid stent placement procedures at the Riverside Methodist Hospital in Columbus, Ohio. The patients all recovered from their procedures without incident and have been discharged from the hospital.

According to the company, the FiberNet embolic protection system is designed to capture and remove embolic material produced while performing interventional procedures in vessels. Delivery of the FiberNet is very similar to advancing a standard .014-inch steerable guidewire, which allows the interventionist to steer the device into difficult to access vessels or past significantly stenosed vessels. The filter is composed of a three-dimensional mesh of polyethylene terephthalate or PET fibers. After the carotid artery stent has been placed, and the FiberNet filter has trapped the associated emboli, the device is retracted into its own retrieval catheter under aspiration, and the entire system is removed from the patient.

"The design of the FilterNet device is significantly different than any other embolic protection system in clinical practice today," commented Dr. Ansel. "It truly appears to be the next generation of advanced distal protection devices. We have been impressed with its agility and flexibility, and have been amazed at the amount of debris that has been trapped and removed."

On July 5, Lumen announced that it received FDA clearance to market its first product in the US, the Xtract Aspiration Catheter, which is indicated for use in the removal of thrombi and soft emboli from vessels throughout the body. According to the company, the Xtract can be used with other devices during vascular intervention procedures. The device is designed to remove fresh, soft emboli, or thrombi from the arterial system. It is a single-use, .014-inch-guidewire-compatible, temporary intravascular extraction, and aspiration catheter system. The Xtract will also be part of Lumen's FiberNet embolic protection system, the company stated.

Study Shows CAS May Reduce Symptoms of Depression
July 25, 2006—Wolfgang Mlekusch, MD, et al at Vienna General Hospital in Austria found that high-grade carotid artery stenosis is associated with depressive symptoms in patients with atherosclerosis and concluded that carotid artery stenting (CAS) seems to exert beneficial effects on the course of depressive symptoms in these patients. The study was published in Radiology (2006;240:508-514). The investigators sought to prospectively evaluate if high-grade internal carotid artery stenosis is associated with depressive symptoms and if CAS potentially improves depressive symptoms. As detailed in Radiology, the study was approved by the local ethics committee, and informed consent was obtained from all subjects. One hundred forty-three patients (91 men, 52 women; interquartile range, 63 to 76 years) undergoing CAS because of asymptomatic high-grade (80% luminal narrowing) carotid artery stenosis and 102 control subjects (64 men, 38 women; interquartile range, 63 to 73 years) with advanced peripheral artery disease and without carotid artery stenosis undergoing lower-limb percutaneous transluminal angioplasty were included. Substantial depressive symptoms (defined as a Beck Depression Inventory score of 10 or higher) were recorded at baseline and at follow-up 4 weeks after the percutaneous procedures. The c2 test, Mann-Whitney U test, McNemar test, Wilcoxon rank sum test, and two-group t test were used to check for statistical significance.

The results demonstrated that a significantly higher prevalence of depressive symptoms was found in patients with carotid artery stenosis than in control subjects with peripheral artery disease at baseline (33.6% vs 16.7%; P=.003). At follow-up, a significant reduction of depressive symptoms was found in patients who underwent CAS (33.6% vs 9.8%; P<.001). The frequency of depressive symptoms remained unaffected in control subjects (16.7% vs 13%; P=.1). Dr. Mlekusch cautioned that while CAS may be able to reduce symptoms associated with vascular depression, it is not a cure or treatment for major depression.

"Our findings suggest that opening the carotid artery and restoring blood flow to the brain via a minimally invasive technique under local anesthesia is associated with significant reduction in depressive symptoms," commented Dr. Mlekusch. "We were able to demonstrate a clear neuropsychological benefit to patients after carotid stenting."

Study Using IVUS Examines Mechanisms and Predictors of CAS Restenosis
June 20, 2006–David J. Clark, MD, et al conducted a study to determine the mechanisms and predictors of carotid artery restenosis after carotid artery stenting (CAS) using serial intravascular ultrasound (IVUS) imaging. The study was based on the fact that, whereas CAS is increasingly used to treat high-grade obstructive carotid disease, knowledge of carotid in-stent restenosis and remodeling remains limited. The investigators published their results in the Journal of the American College of Cardiology (JACC. 2006;47:2390-2396).

As detailed in the JACC, postprocedural and 6-month (median, 6 months) follow-up quantitative carotid angiography and IVUS were performed after self-expanding stent deployment in 50 internal carotid arteries (ICA). The IVUS measurements at multiple designated sites included minimal luminal diameter, lumen area, stent area (SA), and neointimal hyperplasia area (NIH). The results showed that late stent enlargement at follow-up was found at all segments, and the percentage increase was greatest at the ICA lesion site (mean±SD, 48.9±35.3%). The NIH, expressed as a percentage of SA, was seen within all segments of the stent and was greatest at the ICA lesion site (37.3±23.3%). There was a strong positive correlation between the amount of NIH and late stent enlargement (r =.64; P<.001). Immediate postprocedural minimum ICA SA (r=-.37; P<.01) and stent expansion (r =-.44; P=.001) correlated negatively with the percentage restenotic area at follow-up. The investigators concluded that although self-expanding carotid stents generate considerable neointimal hyperplasia, the process is balanced by marked late stent enlargement. Small stent dimensions immediately postprocedure were associated with a higher risk of restenosis, the investigators stated.

Protected Carotid Stenting in High-Risk Patients With Severe Stenosis Studied
June 20, 2006–In a study published in the Journal of the American College of Cardiology (2006;47:2384-2389), Robert D. Safian, MD, et al, on behalf of the CREATE Pivotal Trial Investigators, concluded that for some patients with severe carotid stenosis and high-risk features for carotid endarterectomy (CEA), carotid artery stenting (CAS) with distal embolic protection is a reasonable alternative for revascularization. The investigators stated that the study's purpose was to determine the safety of CAS with a unique distal embolic protection system in high-risk patients with severe carotid stenosis. Previous studies suggest that some patients with carotid stenosis and serious comorbid conditions are at high risk for CEA and may be safely treated by carotid artery stenting, the investigators stated.

In the study, a prospective, nonrandomized, multicenter registry of 419 patients with severe carotid stenosis and high-risk features for CEA was conducted between April 2004 and October 2004. CAS was performed with the Protégé Self-Expanding Nitinol Stent and the Spider Embolic Protection System (ev3 Inc., Plymouth, MN). Aspirin and clopidogrel were prescribed at least 24 hours before and 3 months after revascularization. The primary outcome was the combined incidence of major adverse cardiac and cerebrovascular events at 30 days after intervention, including death, stroke, and myocardial infarction. A secondary outcome was the technical success, defined as successful deployment of all devices, filter retrieval, and final diameter stenosis <50%. The investigators found that technical success was achieved in 408 of 419 patients (97.4%). The primary endpoint was observed in 26 patients (6.2%), including death in eight (1.9%), nonfatal stroke in 14 (3.3%), and nonfatal myocardial infarction in four (1%). Independent predictors of death or stroke at 30 days included duration of filter deployment, symptomatic carotid stenosis, and baseline renal insufficiency, the study result showed.

Kensey Nash Receives Clearance for ThromCat and Completes EPS Carotid Trial
April 27, 2006—Kensey Nash Corporation (Exton, PA) announced that it has completed enrollment of a pilot trial for its TriActiv ProGuard embolic protection system for use in carotid stenting procedures. Data from the study will support a CE Mark. It will also support an IDE submission to the FDA to begin a larger pivotal trial in the US, which is expected to commence during the summer of 2006. Gary S. Roubin, MD, PhD, and Prof. Horst Sievert, MD, served as Principal Investigators for the study, which took place at five centers in the US and Europe and enrolled 50 patients. The TriActiv system is currently indicated to prevent heart attacks during the treatment of saphenous vein grafts in patients who previously received coronary bypass surgery but who now have blockages in the grafts. The TriActiv FX System is commercialized in Europe and has been studied in the 100-patient ASPIRE study registry to support FDA clearance. The TriActiv ProGuard system has received CE Mark for a saphenous vein graft indication, the company stated.

Medtronic Receives CE Mark for Carotid Stent Filter
April 27, 2006—Medtronic, Inc. (Santa Rosa, CA) announced that it has received CE Mark approval for the Exponent RX self-expanding carotid stent. According to the company, the new device, which is not yet approved for use in the US, is part of the Medtronic Carotid Solution, which also includes the Interceptor Plus carotid filter system. The first procedures using the new stent and filter were performed by Alberto Cremonesi, MD, and Fausto Castriota, MD, at the Villa Maria Cecilia Hospital in Cotignola, Italy; and by Carlo Setacci, MD, at University Hospital Santa Maria alle Scotte in Siena, Italy.

"The Medtronic Carotid Solution offers excellent performance in diverse clinical situations," commented Dr. Setacci. "The Exponent stent conforms and adapts very well to the carotid anatomy, and the Interceptor filter is designed to capture dangerous embolic debris as it maintains blood flow during the procedure. These characteristics give me great confidence that I can treat my patients safely and efficiently."

Carotid Artery Stenting Supported By CASES-PMS and CAPTURE 3000 Registry Data
March 14, 2006—Results of postmarketing studies from Cordis Endovascular (a division of Cordis Corporation, a Johnson & Johnson company, Warren, NJ) and from Guidant Corporation (Indianapolis, IN) testing the safety of carotid artery stenting (CAS) in high-risk patients demonstrated that interventionists from multiple specialties who undergo a formalized training program can perform CAS and achieve excellent results. The studies were presented in seperate lectures at the American College of Cardiology's 55th Annual Scientific Session, which was held on March 11-14 in Atlanta. Theodore L. Schreiber, MD, presented Cordis's Carotid Artery Stenting With Emboli Protection Surveillance-Post-Marketing Study (CASES-PMS). William A. Gray, MD, presented Guidant's Carotid Acculink/Accunet Post-Approval Trial to Uncover Unanticipated or Rare Events (CAPTURE 3000) Registry.

CASES-PMS is a multicenter, prospective, single-arm, open-label periapproval study designed to assess the outcomes of stenting with Cordis's investigational Precise Nitinol Self-Expanding Stent and the company's investigational Angioguard XP Emboli Capture Guidewire System in the treatment of obstructive artery disease in relation to the outcomes of the pivotal study, Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE). The primary objective of CASES-PMS is to demonstrate that outcomes in a periapproval setting, including use of a detailed training program in CAS for physicians not experienced in CAS, allow outcomes that are similar to those obtained in the pivotal trial setting. According to the company, these initial results both corroborate the findings of the SAPPHIRE study, and demonstrate that formalized training in CAS allows physicians from multiple specialties with prior endovascular experience to perform CAS and obtain outcomes as good as the experts who performed the clinical trials. Cordis Endovascular initiated CASES, its comprehensive training program for physicians and other relevant health care professionals, in 2004. The training includes didactic review, case observations and simulation training, and hands-on experience at the CASES regional education centers across the country.

According to Cordis, the preliminary results from CASES-PMS showed that high surgical-risk patients treated with CAS had 30-day major adverse event (MAE) rates identical with that of patients treated with CAS in SAPPHIRE. The data showed an MAE rate of 4.8% (62/1279) among patients treated with CAS in CASES-PMS compared with 4.8% (8/167) of CAS-treated patients in the randomized arm of the SAPPHIRE trial. Overall, the rate of stroke at 30 days was 3.6% (46/1279), whereas the rate of stroke in patients treated by physicians who completed the entire training program was 3.7% (3/82). CASES-PMS enrolled 1,493 patients at more than 70 sites in the US; preliminary data presented at ACC was on the first 1,279 enrolled patients. The study enrolled high surgical-risk patients with de novo atherosclerotic or postendarterectomy restenotic obstructive lesions in native carotid arteries. Inclusion and exclusion criteria matched those in the SAPPHIRE study. Clinical follow-up was conducted at 30 days, and will be conducted again at 1 year postprocedure. The 30-day assessments include a neurological examination and an evaluation of adverse events. The 30-day MAE rate was defined as the 30-day composite of all death, myocardial infarction, and stroke. Clinical events at 1 year also will be assessed.

In Guidant's CAPTURE 3000 Registry, Dr. Gray and his colleagues collected data on more than 3,000 patients treated by 240 interventionists at 118 medical centers throughout the US as part of the FDA-required postapproval study of the company's Rx Acculink carotid stent system and Rx Accunet embolic protection system. According to the company, the goal of the ongoing CAPTURE 3000 Registry is to evaluate rare or unanticipated events among patients treated with carotid stenting using the Acculink/Accunet devices. The present analysis included the first 2,500 patients in the registry. Symptomatic disease was present in 9.3% of patients, 34% had diabetes, and 20% were smokers. Of the physicians, 71% had performed at least 10 carotid stent procedures as the primary operator. At 30 days, death, stroke, or MI had occurred in 5.7% of patients. Among the components of the composite event rate, death had occurred in 1.6%, stroke in 4.2%, and MI in 0.9% patients. Among the cohort of asymptomatic patients (n=2,267), the composite event rate was 4.9%, with death in 1.3%, stroke in 3.5%, and MI in 0.7% of patients. Among the cohort of symptomatic patients (n=233), the composite event rate was 14.2%, with death occuring in 4.3%, stroke in 11.2%, and MI in 2.6% of patients. Event rates were higher in patients aged greater than or equal to 80 years with a composite rate of 8.2%, and death in 2%, stroke in 6.6%, and MI in .5% patients.

"The transfer of carotid stenting technology from clinical trial sites to clinical practice sites appears to have been successful with the same, or even better, outcomes in the clinical setting," commented Dr. Gray.

On March 17, Guidant announced that the first patient has been enrolled in the company-sponsored CAPTURE 2 postapproval study of CAS with the Acculink/Accunet systems in high-surgical risk patients. A key objective of the study is to gather additional and more extensive clinical data to extend Medicare coverage of carotid stenting to a broader group of patients. The study will include up to 10,000 patients at 400 US centers. According to the company, data from CAPTURE 2 will provide a deeper and broader understanding of carotid stenting in real-world clinical settings with physicians who enter Guidant's training program with varying levels of experience, and will examine outcomes in both symptomatic and asymptomatic patients. The study will use an innovative electronic data capture system to collect the rate of death, stroke, and MI at 30 days after the procedure. Guidant will work with Dartmouth Medical School and the CMS to link to the Medicare database to collect 1-year patient outcomes. An executive committee made up of physicians from multiple specialties will oversee the trial.

CAS Shows Significant Benefits for Asymptomatic Patients in Study
March 31, 2006—The Society of Interventional Radiology (SIR) announced that a study involving the most comprehensive measurement of pre- and postneurocognitive effects of carotid artery stenting (CAS) found that patients classified as "asymptomatic" and "symptomatic" both had statistically significant improvement in brain function after being treated with CAS. Rodney Raabe, MD, presented the study at SIR's 31st Annual Scientific Meeting, which was held on March 30-April 4 in Toronto. The study also showed that using an embolic protection filter is beneficial and saved patients from neurocognitive decline during CAS procedures. The study used the RX Acculink carotid stent system and the RX Accunet embolic protection system (Guidant Corporation, Indianapolis, IN). Forty nonrandomized patients with symptomatic (>70%) stenosis and asymptomatic (>80%) stenosis by NASCET criteria and who were at high-surgical risk for carotid endarterectomy underwent carotid angioplasty and stenting with distal protection.

The investigators stated that they sought to evaluate neurocognitive changes after CAS with distal protection while testing the hypothesis that CAS with filter protection can prevent a neurocognitive deficit due to embolization. Neurocognitive measurements included IQ, handling of spatial relationships, memory, and other executive functions. These functions were tested in each patient five times before and four times after the procedure. The tests included the ability to respond to a command, integrating the command, and providing an answer in return. Word memory, number memory, and ability to put things in order were also tested. These functions improved, even in patients with a lower degree of stenosis, and the improvement was statistically significant. These are interim results and analysis of 26 patients at 6 months in this ongoing study.

Patients were assessed with a battery of five standard neurocognitive tests that assess memory, attention, and depression. Patients completed neurocognitive batteries prior to stenting (baseline) within 2 days, and at 3, 6, and 12 months postsurgery. Data were evaluated with repeat-measure ANOVA (analysis of variance) and residualized change scores while modeling for covariates of attention, degree of stenosis at baseline, age, and history of previous stroke/TIA.

The study results showed that scores over time were seen to interact with age and history of previous stroke/TIA. Improvement was seen in DRS (Dementia Rating Scale)-Concept Formation, NAART (North America Adult Reading Test) errors, and RAVLT (Ray Auditory Verbal Learning Test) Recognition Memory scores. For those without a history of previous stroke/TIA, the younger group (<71 years) showed improvement in the DRS-2 concept subscale by 3 months while the more elderly group showed a decrease in their concept score at 3 months with recovery to baseline levels by 6 months. One patient experienced a TIA involving the contralateral hemisphere less than 24 hours after the intervention. There were no major strokes or deaths. The investigators concluded that the data indicate a trend for cognitive benefit when undergoing CAS with a distal protection device. They postulated that patients with carotid stenosis have neurocognitive impairment that improves with CAS

According to the SIR, the results show that asymptomatic patients with narrowed carotid arteries were, in fact, having neurocognitive deficits involving executive functions and memory, and that these deficits improved after CAS. The study indicates that patients could benefit from being treated earlier in their disease progression than currently thought. The procedure improved brain function in symptomatic patients, but asymptomatic patients had the most significant gain. It was also noted that younger patients had the greatest gains in neurocognitive function, most likely because they had more neurocognitive reserve and had not suffered previous injury to the brain from strokes or TIAs. The improvement was due to the restoration of blood flow to the brain through the carotid artery, as shown on MRI after the procedure. Dr. Raabe noted in his presentation that the collateral blood flow around the carotid artery before the CAS procedure was not sufficient to maintain the patients' neurocognitive function.

"We set out to show that the protection filter would protect the brain, and expected to prove it by showing that the patient's brain function did not worsen after carotid stenting," commented Dr. Raabe. "We never expected to see brain function improve. These patients are seeing better and thinking better, and those with the least degree of disease had the greatest gain."

FDA Clears ev3's SpideRX for Carotid Stenting
February 17, 2006—ev3 Inc. (Plymouth, MN) announced that the FDA has granted 510(k) clearance for the SpideRX Embolic Protection Device for use in carotid artery stenting applications. ev3 plans an immediate market release of the SpideRX, which is already commercially available in Europe and several countries in Latin America and Asia. The SpideRX device, which features a nitinol filter to capture embolic debris, is designed to provide efficient delivery, capture, and recovery while allowing interventionists to use their interventional wire of choice.

Improvements from the Spider over-the-wire system include a complete rapid exchange system, 6-F guide catheter compatibility, and a dual-end delivery/recovery catheter with a preloaded capture wire, the company said.

According to the company, the FDA clearance was supported by a 160-patient, high-risk carotid stent registry as part of ev3's CREATE Carotid Registry. CREATE also included a 419-patient arm studying the Protege GPS self-expanding stent and the Spider over-the-wire device. This arm of the study was designed to evaluate the SpideRX rapid-exchange embolic protection device for use with the Guidant RX Acculink (Guidant Corporation, Indianapolis, IN) carotid stent system. The primary endpoint was defined as 30-day major adverse cerebrovascular and cardiovascular events (MACCE) including myocardial infarction, ipsilateral cerebrovascular accident (CVA), procedure-related contralateral CVA, or death. MACCE at 30 days for the SpideRX arm occurred in 5.6% of patients.

"The CREATE Trial data confirms the success and safety of the SpideRX device for use in carotid stenting of patients at increased surgical risk," commented Gary Ansel, MD, Co-Principal Investigator for the CREATE trial. "The SpideRX device is unique in that it allows physicians to utilize their own wire system of choice, leading to consistent success in placing the embolic protection device during carotid interventions."

Carotid Intima-Media Thickening Indicates Vascular Risk in Young and Old Alike
January 1, 2006—In the Carotid Atherosclerosis Progression Study (CAPS), Matthias W. Lornenz, MD, et al concluded that the predictive value of carotid intima-media thickness (IMT) for future vascular events is at least as high in younger patients as in older patients (Stroke. 2006;37:87-92). Noting that there is little information about the predictive value of IMT in younger individuals, the CAPS investigators evaluated common carotid artery (CCA) IMT, bifurcation IMT, and vascular risk factors at baseline and prospectively determined the incidence of stroke, myocardial infarction (MI), and death in 5,056 patients who ranged in age from 19 to 90 years (mean, 50.1 years).

As detailed in Stroke, data for younger (<50 years; n = 2,436) and older subjects (>50 years; n = 2,620) were analyzed separately using Cox proportional hazard regression models. The investigators found that during a mean follow-up period of 4.2 years, there were 228 cases of MI, 107 strokes, and 50 deaths. IMT at all carotid segments was highly predictive of all end points. Hazard rate ratios (HRRs) per 1 SD CCA-IMT increase were 1.43 (95% CI: 1.35 to 1.51) for MI, 1.47 (1.35 to 1.60) for stroke, and 1.45 (1.38 to 1.52) for MI, stroke or death; all P<.0001. Even after adjustment for age, sex, and vascular risk factors, the predictive value of CCA-IMT and bifurcation IMT remained significant for MI and the combined end point. For the latter, the HRRs were considerably higher in the younger than in the older age group (HRR per .1-mm CCA-IMT was 1.34 (1.16 to 1.55) vis-à-vis 1.1 (1.05 to 1.15); P = .011 for age-IMT interaction), reported the CAPS investigators.

2005

ev3 Announces CREATE I and II Clinical Trial Results
November 1, 2005—ev3, Inc. (Plymouth, MN) today announced that results from the CREATE I Carotid Stent Trial utilizing ev3's Spider Embolic Protection Device with the Protege GPS Self-Expanding Stent, and the CREATE II Carotid Stent Trial utilizing ev3's next-generation SpideRX Embolic Protection Device with the AccuLinkRX Stent (Guidant Corporation, Indianapolis, IN) were presented at the 17th Annual Transcatheter Cardiovascular Therapeutics (TCT 2005) Scientific Symposium in Washington, DC. The trials were conducted in accordance with an FDA Investigational Device Exemption.

According to the company, Co-Principal Investigators Robert Safian, MD, and Gary Ansel, MD, conducted the CREATE I and II clinical trials to evaluate the safety and efficacy of the ev3 Spider and SpideRX Embolic Protection Devices and the Protege GPS Self-Expanding Stent for the minimally invasive, endovascular treatment of high-risk patients with carotid artery disease. The Spider device and the Protege stent met the safety and efficacy endpoints in the 419-patient CREATE I registry. Likewise, the SpideRX Embolic Protection Device used with the Guidant AccuLinkRX Stent met its safety and efficacy endpoints in the 160-patient CREATE II registry trial. These data will be submitted to the FDA in support of the product's approval, the company said.

In other company news, on November 14, ev3 and Micro Therapeutics, Inc. (MTI, Irvine, CA) announced that they have entered into an agreement pursuant to which a wholly owned subsidiary of ev3 would be merged with MTI. ev3, which currently owns approximately 70.1% of MTI's common stock through a wholly owned subsidiary, would acquire all MTI shares that it does not presently own in a tax-free transaction. As a result of the execution of the merger agreement, ev3 no longer intends to commence the previously announced exchange offer for the MTI shares that it does not own. According to the companies, under the merger agreement, MTI stockholders would receive 0.476289 of a share of ev3 common stock for each share of MTI common stock that they own. This exchange ratio represents a 4% increase in the number of ev3 shares to be issued to each MTI stockholder from the proposed exchange ratio announced on October 10, 2005, in connection with ev3's initial proposal to MTI. The transaction, which is otherwise subject to customary conditions, is expected to be completed in the first quarter of 2006.

Carotid Trials Will Study Kensey Nash's TriActiv System
November 3, 2005—Kensey Nash Corporation (Exton, PA) announced the commencement of a trial of the new version of the TriActiv Embolic Protection System for carotid stenting procedures in a European pilot study. Horst Sievert, MD, of Frankfurt, Germany, is serving as Principal Investigator. The study will support a CE Mark application, expected in 2006, for use of the TriActiv Embolic Protection System during carotid stenting procedures. The company also announced FDA approval of its IDE submission to commence a similar feasibility study in the US, which is scheduled to start by the end of this month.

According to the company, the trials utilize the new version of Kensey Nash's TriActiv System product line, which incorporates Local Flush and eXtraction (LFX) technology designed for use in branched arteries. The TriActiv ProGuard System incorporates three features designed to reduce the incidence of embolic stroke during carotid stenting procedures—a balloon protection guidewire, a flush catheter, and an automated extraction system to remove debris. The system will be studied and can be used in combination with any approved stent, the company stated.

Absence of Microemboli on Transcranial Doppler Identifies Low-Risk Patients With Asymptomatic Carotid Stenosis
November 1, 2005—Findings of a Canadian study by J. David Spence, MD, et al (Stroke. 2005;36:2373-2378) suggest that asymptomatic patients should be managed medically, with delay of surgery or stenting until the occurrence of symptoms or emboli. Although carotid endarterectomy clearly benefits patients with symptomatic severe stenosis, the investigators began their research noting that the risk of stroke is so low for asymptomatic patients that the number needed to treat in order to prevent a stroke is very high.

The investigators studied transcranial Doppler embolus detection as a method for identifying patients at higher risk who would have a lower number needed to treat to prevent a stroke. Patients with carotid stenosis of 60% by Doppler ultrasound, who had never been symptomatic (81%) or had been asymptomatic for at least 18 months (19%), were studied with transcranial Doppler embolus detection for up to 1 hour on two occasions a week apart; patients were followed for 2 years. Of the 319 patients studied, 32 (10%) had microemboli at baseline. Events were more likely to occur in the first year. Patients with microemboli were much more likely to have microemboli 1 year later (34.4% vs 1.4%) and were more likely to have a stroke during the first year of follow-up (15.6% vs 1%) than patients without microemboli.

According to the investigators, their findings indicate that asymptomatic patients without microemboli as determined by transcranial Doppler will not benefit from endarterectomy or stenting unless it can be done with a risk <1%. Asymptomatic patients with microemboli as determined by transcranial Doppler may benefit as much as symptomatic patients if their surgical risk is not higher.

Early CAPTURE Results Suggest That CAS Therapy Can Be Performed Safely By a Broad Group of Endovascular Specialists
October 20, 2005—At the 17th Annual Transcatheter Cardiovascular Therapeutics (TCT 2005) Scientific Symposium in Washington, DC, Jay S. Yadav, MD, presented preliminary results of CAPTURE (Carotid Acculink/Accunet Postapproval Trial to Uncover Rare Events). CAPTURE is a study of carotid artery stenting in high-risk patients sponsored by Guidant Corporation (Indianapolis, IN). CAPTURE is an FDA-required postapproval study utilizing Guidant's RX Acculink Carotid Stent System and RX Accunet Embolic Protection System. Key objectives of CAPTURE were to determine whether carotid artery stenting can be performed safely in real-world clinical settings with physicians of varying levels of experience and to evaluate the effectiveness of Guidant's training program.

According to the company, the initial results of the study confirm positive earlier data on carotid stenting for high-risk patients. In addition, the study suggests that physicians of different experience levels can safely perform carotid artery stenting. The rate of death, stroke, and myocardial infarction within 30 days of the procedure was 5.1%. Results were based on data from 1,603 patients receiving the Acculink and Accunet systems, which are indicated for high-surgical-risk patients. Two hundred forty physicians, including interventional cardiologists, interventional radiologists, interventional neuroradiologists, vascular surgeons, and neurosurgeons, treated patients at 118 hospitals in the US. CAPTURE has enrolled more than 2,800 patients to date and continues to enroll. Guidant is also participating in the CREST trial, which is evaluating carotid artery stenting in low-surgical-risk patients.

"CAPTURE is a landmark study," commented Dr. Yadav. "It demonstrates, for the first time, that with proper training, carotid stenting can be performed with exemplary results by a variety of physicians in community hospital settings."

Enrollment Initiated in Bard's VIVA Carotid Stent Trial
October 20, 2005—Bard Peripheral Vascular, Inc., a subsidiary of C. R. Bard, Inc. (Murray Hill, NJ), announced the start of its Vivexx Carotid Revascularization Trial (VIVA), a prospective, multicenter, nonrandomized registry of 400 patients at up to 50 US sites. The trial is designed to evaluate the safety and efficacy of the Bard Vivexx Carotid Stent with an FDA-approved embolic protection system to treat extracranial carotid stenosis in patients at high risk for carotid endarterectomy. The investigators expect that enrollment in this IDE trial will proceed quickly over the next several months, stated the company.

According to Bard, the VIVA trial's Co-Principal Investigators, representing each of the primary clinical specialties performing carotid artery stenting, are interventional cardiologist Kenneth Rosenfield, MD; neurovascular surgeon L. Nelson Hopkins, MD; and, interventional radiologist Barry T. Katzen, MD. Rajesh Dave, MD, successfully treated the first patient enrolled in the VIVA Trial at Harrisburg Hospital (Harrisburg, PA). The patient, who had undergone previous bilateral endarterectomy, was suffering from a 90% restenosis that was treated with a tapered Vivexx Carotid Stent, with no residual stenosis on final angiogram. "I believe the low-profile, monorail device will excel in the treatment of carotid artery disease and that the 5-F compatibility allowed for exceptional contrast injection through a 6-F sheath," said Dr. Dave.

"We are very excited that the Bard VIVA carotid trial is underway," said Dr. Rosenfield. Dr. Hopkins added, "The flexibility and excellent conformability of the Vivexx Carotid Stent, when combined with an FDA-approved embolic protection system, make this stent a potentially valuable weapon in the war against stroke."

Three-Year SAPPHIRE and US Carotid Feasibility Trials Demonstrate Durability of Carotid Stenting
October 18, 2005—Cordis Corporation (a Johnson & Johnson company, Miami, FL) announced that preliminary 3-year data from the SAPPHIRE trial and the final 3-year data from the US Carotid Feasibility Study (USFS) were presented at the 17th Annual Transcatheter Cardiovascular Therapeutics (TCT 2005) Scientific Symposium in Washington, DC. Cordis sponsored both SAPPHIRE and the USFS. According to the company, the results demonstrate the long-term durability of carotid artery stenting (CAS) for the prevention of stroke versus carotid endarterectomy (CEA) in high-surgical-risk patients.

In the SAPPHIRE trial, 334 patients were randomized to either CAS or CEA. Patients who received CAS with the Cordis Precise Nitinol Self-Expanding Stent and the Cordis Angioguard XP Emboli Capture Guidewire System maintained a low incidence of stroke after the first 30 days for the duration of the 3-year follow-up in the USFS and SAPPHIRE. At 36 months, the incidence of stroke was 7.1% for CAS and 6.7% for CEA. The 3-year incidence of stroke across the randomized and nonrandomized CAS treatment groups in SAPPHIRE and the USFS had an average increase of 4% over the 30-day stroke rate. An analysis of target lesion revascularization with follow-up to 3 years in the randomized arms of SAPPHIRE showed reintervention rates of 3% for CAS and 7.1% for CEA. Three-year target lesion revascularization rates for CAS were similar in the USFS, the company stated.

"The SAPPHIRE trial demonstrated CAS was noninferior to CEA," commented Jay S. Yadav, MD, a principal investigator for SAPPHIRE. "This is important new data which suggests the long-term durability of CAS in this patient population." Cordis further announced that in two poster sessions at TCT 2005, data from the SAPPHIRE, USFS, and CASCADE clinical trials suggest that emboli protection is effective in preventing major strokes during CAS. Thirty-day stroke rates were 8.6% for the 266 patients treated with stenting alone and 2.6% for the 116 patients treated by stenting with Cordis's Angioguard system. No patients treated with an Angioguard in CASCADE, USFS, or in the treated randomized portion of SAPPHIRE had a major stroke. Approximately two-thirds of the minor ipsilateral strokes that occurred in the trials resolved with time, according to the company.

FDA Approves Abbott's Xact Carotid Stent; Emboshield Cleared for Carotids
September 15, 2005—Abbott Vascular (Redwood City, CA) announced that it has received FDA approval for the Xact Carotid Stent and 510(k) clearance for the Emboshield Embolic Protection System to treat patients at risk for stroke who are not favorable candidates for surgery.

According to the company, the Xact is a self-expanding stent designed specifically to treat diseased carotid arteries; the device has a closed-cell design that creates a tightly knit yet highly flexible mesh structure intended to help restore the inner diameter of the artery, promote a smooth inner vessel surface, and potentially reduce the release of emboli from a diseased vessel when it is treated. The Xact stent is intended for use in combination with the fully retractable Emboshield filter, which is designed to capture emboli that can break off during a carotid stenting procedure. A unique feature of the Emboshield is the use of Barewire, a proprietary technology developed to allow for better control of stent placement once the filter is in place and fully apposed against the vessel wall, the company said.

Abbott is currently conducting ACT I (Asymptomatic Patients with Significant Extracranial Carotid Occlusive Disease Trial), a multicenter, randomized trial to compare the safety and effectiveness of carotid artery stenting with carotid artery surgery, using the Xact and Emboshield.

"Carotid endarterectomy has proven to be a reliable method for treating carotid artery disease, but it is not the ideal treatment for everyone," commented Gary S. Roubin, MD, PhD, of Lenox Hill Hospital in New York. "The Xact Carotid Stent and Emboshield Embolic Protection System provide a truly advanced minimally invasive treatment alternative for these patients.".

Kensey Nash Seeks IDE for TriActiv LFX System in Carotid Stenting Trial in US
September 23, 2005—Kensey Nash Corporation (Exton, PA) announced that it has submitted an IDE application to the FDA to study the use of a new version of the TriActiv Embolic Protection System platform for use during carotid stenting procedures. The company expects to begin a pilot trial at a limited number of sites in the US within 90 days pending regulatory approval.

According to the company, the trial will utilize the newest version of the TriActiv System, which incorporates Local Flush and eXtraction (LFX) technology designed for use in branched arteries, such as those of the carotid blood vessels. If successful, the company said it will plan a larger pivotal trial to support clearance for the US market. The TriActiv System incorporates three features designed to reduce the incidence of embolic stroke during carotid stenting procedures: a balloon protection guidewire, a flush catheter, and an extraction system to remove debris.

"I believe the new TriActiv System with its LFX technology has the potential to change the treatment paradigm for treating carotid artery disease," commented the registry's Principal Investigator, Gary S. Roubin, MD, PhD, of Lenox Hill Hospital in New York. "My experience with the TriActiv System platform has convinced me that it will be easy to use and more effective when tackling the challenges of carotid stenting procedures.".

CABERNET Trial Demonstrates Favorable Outcomes in High-Risk Patients
May 26, 2005—EndoTex Interventional Systems, Inc. (Cupertino, CA) has announced favorable results of the CABERNET trial. The CABERNET Trial is a prospective, nonrandomized, multicenter, single-arm clinical study performed to demonstrate the safety and efficacy of the EndoTex NexStent Carotid Stent System and the Boston Scientific Corporation (Natick, MA) FilterWire EX/EZ Embolic Protection Systems when used to treat high-risk, surgical and nonsurgical, symptomatic (≥50% stenosis) and asymptomatic (≥80% stenosis) subjects with disease in the internal carotid artery. A total of 454 patients were enrolled at 19 clinical sites (15 in the US and four outside the US).

The composite major adverse events rate at 1 year, defined as any death, stroke, or MI ≥30 days postprocedure plus any ipsilateral stroke, including any death as a result of an ipsilateral stroke from 31 days to 365 days, was 4.5% (death = 0.5%; stroke = 4%; MI = 0.2%). "The exceptional results from the CABERNET Trial clearly exceeded our expectations," said Principal Investigator L. Nelson Hopkins, MD, Professor and Chairman of Neurosurgery at the University of Buffalo, State University of New York. "These results compare very favorably with other similar US high-risk CAS trials and appear competitive with the major CEA trials."

EndoTex has received CE Mark approval for the NexStent, and expects to file US premarket approval application with the FDA in the near future.

One-Year Data of BEACH Trial Revealed at All That Jazz
April 27, 2005—Boston Scientific Corporation (Natick, MA) announced 1-year data from its carotid artery stenting (CAS) clinical trial known as BEACH. The study evaluates the effectiveness of stenting with embolic protection for patients who are at high-risk for carotid endarterectomy (CEA). The trial's Co-Principal Investigator, Christopher White, MD, of the Ochsner Heart and Vascular Institute, presented results at the 14th Annual Peripheral Angioplasty and All That Jazz meeting in New Orleans.

According to the company, the BEACH trial was designed to evaluate Boston Scientific's Carotid Wallstent Monorail Endoprosthesis (Carotid Wallstent) and the FilterWire EX and EZ Embolic Protection Systems. It is a prospective, nonrandomized, single-arm clinical trial that enrolled 747 patients at 47 US sites, with 480 patients in the pivotal phase of the trial. The trial also enrolled 189 patients in a "roll-in" group and 78 patients in a bilateral registry. The composite primary endpoint is cumulative mortality and morbidity through 1 year, consisting of stroke, death, and myocardial infarction (MI). Dr. White presented data showing a composite 1-year endpoint of 9.1%. The breakdown of patients experiencing one or more events is: stroke, 7%; death, 3.2%; and MI, 1.1%.

Event rates were similar for the roll-in group and bilateral registry. The roll-in group (in which physicians trained on the Boston Scientific devices before entering the pivotal group) reported an event rate of 8.7%. The bilateral group reported an event rate of 7.1%. According to the company, the BEACH results suggest that CAS may ultimately be a viable treatment option for this high-risk population.

"These results are well within the trial objectives we hoped to meet," said Dr. White. "They suggest that carotid artery stenting with embolic protection is a viable treatment option in the high-risk patients represented by this study. The roll-in results suggest there is a minimal additional learning curve in this complex patient subset, which is important information when planning physician training and ensuring patient safety."

The company notes that the devices have independently received CE Mark and are commercially available in Europe and certain other international markets. The Carotid Wallstent is an investigational device in the US and is limited by federal law to investigational use. The company further states that the safety and effectiveness of the FilterWire EZ and EX Embolic Protection Systems for use in carotid arteries has not been established in the US and is currently investigational.

CMS Expands Coverage of CAS for Patients at High Risk for Surgery
March 17, 2005—The Centers for Medicare & Medicaid Services (CMS) is expanding coverage of percutaneous transluminal angioplasty (PTA) of the carotid artery concurrent with stent placement to patients who are at high risk for carotid endarterectomy (CEA). The coverage is effective immediately. According to CMS, the coverage expansion reflects the latest evidence on the effective use of stenting and includes support for development of better evidence in additional uses. The final decision memorandum is available for review at www.cms.hhs.gov/coverage.

The national coverage determination expands Medicare coverage for carotid artery stenting to high-risk patients with symptomatic narrowing of the carotid artery of 70% or more. Medicare also will cover patients who meet the FDA-labeled criteria for carotid stents (ie, who are at high risk for CEA and have symptomatic carotid artery stenosis between 50% and 70%, and asymptomatic high-risk patients with carotid artery stenosis of 80% or more) in Category B IDE clinical trials, as a routine cost under the clinical trials policy, or in postapproval studies.

Medicare is limiting use of carotid stenting to facilities and providers who have been determined to be competent in performing the evaluation, procedure, and necessary follow-up care. Competency will be based on published clinical guidelines that outline physician training and facility support requirements for carotid artery stenting. Facilities must also meet the CMS minimum standards in performing carotid artery stenting. These standards, outlined in the coverage determination, include physician training criteria, facility support requirements, and data collection to evaluate outcomes during a required re-evaluation. Facilities can provide a written affidavit to CMS attesting that the facility has met these standards.

CMS noted that Guidant Corporation (Indianapolis, IN) is currently the only company with an FDA-approved carotid stent and an ongoing postapproval study. CMS and Guidant Corporation are working with the FDA to expand the scope of postapproval studies and increase the number of participating facilities and study enrollees.

Bilateral, Simultaneous CAS Is Safe and Effective in Study
February 28, 2005—Fast-tracking high-risk patients by opening both carotid arteries in the same stenting procedure is a safe and effective alternative to waiting, suggests a new study published in the March 2005 issue of Catheterization and Cardiovascular Interventions: Journal of the Society for Cardiovascular Angiography and Interventions.

To evaluate the safety of simultaneous carotid stenting, Michel Henry, MD, and colleagues at Cabinet de Cardiologie in Nancy, France, analyzed the medical records of 57 high-risk patients with severe stenosis of the carotid arteries on both sides of the neck. Before the procedure, 70% of patients were having neurological symptoms, such as mini-strokes. Nearly two-thirds had severe narrowing in the arteries of the heart. The combined rate of stroke, death, and heart attack was 11.7% in patients who underwent simultaneous carotid artery stenting, as compared to 7.4% in patients who underwent a two-stage procedure. When data were combined for patients who had a simultaneous procedure or a two-stage procedure within 24 hours, the combined rate of stroke, heart attack, and death was 7.4%. The authors note that because some of the procedures were performed as early as 1995, 15 of the 57 cases were performed before current advanced devices in clot protection were available. "Careful patient and lesion selection, as well as routine use of cerebral protection, should improve the outcomes of this technique," Dr. Henry said. "Performing the second angioplasty the day after the first procedure seems to be another promising option."

2004

Gore Acquires ArteriA, Carotid Anti-Embolization Technology
November 18, 2004—W.L. Gore & Associates (Flagstaff, AZ) has acquired substantially all of the assets of ArteriA Medical Science, Inc. (San Francisco, CA). ArteriA manufactures the Parodi Anti-Emboli System (PAES and PAES II) and other related devices. Developed with Juan C. Parodi, MD, ArteriA's PAES employs patented flow reversal technology for use during carotid revascularization to minimize the risk of clinical complications such as stroke. With PAES, Gore expands its endovascular product portfolio into neurointerventional clinical applications.

The PAES is commercially available to physicians in Europe and elsewhere outside the US. In the US, the PAES is limited to investigational use. An FDA IDE clinical study is in progress.

The PAES is a guiding catheter with an elastomeric balloon that is inflated in the common carotid artery proximal to the stenotic lesion and a hollow wire with an elastomeric balloon at its tip to occlude the external carotid artery. An outside connector with a filter creates an external arteriovenous fistula (by connecting sideport of the arterial and venous introducers). During active flow reversal, embolization can be avoided. Dr. Parodi explained, "This system is designed for patients with tortuous internal carotid arteries where filter devices cannot be used. Further, it is also expected that the system will facilitate retrieval of all the particles, irrespective of their size." According to Gore, the PAES may allow physicians to treat patients with carotid artery disease who previously were unsuitable for endovascular therapy.

CMS Proposes Expansion of CAS PTA Coverage
December 17, 2004—CMS has proposed expanded coverage of percutaneous transluminal angioplasty (PTA) of the carotid artery concurrent with stent placement in patients who are at high risk for carotid surgery. The proposed Medicare coverage is restricted to high-risk patients with symptomatic narrowing of the carotid artery of 70% or more. Patients at high risk for CEA are defined as having significant comorbidities and/or anatomic risk factors (ie, recurrent stenosis and/or previous radical neck dissection), and would be poor candidates for CEA in the opinion of a surgeon. Coverage will also be made available to asymptomatic high-risk patients who are enrolled in prospective clinical studies. In a statement, CMS said that the proposed coverage will limit use of carotid stenting to facilities and providers who have been determined to be competent in performing the evaluation, procedure, and necessary follow-up care. This will help ensure optimal patient outcomes and will allow for evaluation and monitoring of provider and facility performance, CMS said.

CMS currently covers PTA of the carotid artery concurrent with stent placement only in Category B Investigational Device Exemption (IDE) clinical trials being conducted prior to FDA approval and, recently, in FDA postapproval studies. CAS to treat indications not included in this expansion of coverage, such as asymptomatic carotid stenosis or symptomatic disease with less narrowing (50%-70%) are still eligible for coverage under the Category B IDE policies.

The proposed new coverage policy is available for review at the CMS coverage Web site (www.cms.hhs.gov/coverage). CMS's 30-day public comment period runs from December 17, 2004, to January 17, 2005. CMS is particularly interested in comments on the following: appropriate criteria, comorbid or chronic conditions for defining patients at high risk for CEA; criteria for appropriately defining symptomatic patients; professional and facility standards for performing PTA of the carotid artery with carotid stent placement; and, evaluation process for providers and facilities. Instructions for submitting public comments are available at www.cms.hhs.gov/coverage/8h.asp. After the close of the comment period, CMS will have 60 days to review the comments and issue a final policy.

Cordis Begins CAS Surveillance Study, Launches Physician Training Program
September 27, 2004—Cordis Endovascular (a Johnson & Johnson company, Miami, FL) has enrolled the first patient in the surveillance study for the company's carotid artery stenting system. The launch of this study follows the approvable letter that Cordis received in August from the FDA for the Precise Nitinol Self-Expanding Stent, part of the Cordis Carotid System. The company reports that the FDA will review separately the second-generation embolic protection device, the Cordis AngioGuard XP Emboli Capture Guidewire System, the second component of the Cordis Carotid System, under a 510(k) process. Cordis is currently working closely with the FDA to fulfill requirements for final marketing approval of Cordis Precise and Cordis AngioGuard.

The surveillance study is designed to provide ongoing data about the carotid stenting procedure. When fully implemented, it will enroll 1,500 patients at 112 US sites. Cordis states that these centers are being selected based on criteria agreed upon by the FDA and will represent a cross section of the physicians who will be performing the procedure.

As part of the surveillance study, the FDA also granted permission to Cordis to launch CASES (Cordis Carotid Artery Stenting Education System)--the company's training program for physicians and other relevant healthcare professionals. The program will include didactic review, case observations and simulation training, and hands-on experience at one of the Regional Education Centers across the country. The program was developed by a group of thought leaders and was reviewed by the FDA and CMS.

CABERNET and MAVErIC Trial Updates Presented at TCT
October 5, 2004—Results from ongoing clinical trials of carotid artery stenting (CAS) continue to show comparable efficacy to previous and ongoing trials of similar devices, according to investigators presenting data from CABERNET and the MAVErIC trials at last week's TCT meeting. In the Late-Breaking Clinical Trials session, L. Nelson Hopkins, MD, of the State University of New York, presented the 30-day results for the pivotal group in the CABERNET trial, and Stephen Ramee, MD, of the Ochsner Clinic Foundation, presented the 1-year results of MAVErIC I and the 30-day results of MAVErIC II. Both presenters remarked that composite endpoint statistics were favorable and slightly lower than those observed in previous CAS trials, and that perhaps declining MACE rates may indicate that user proficiency continues to improve, as many of the same investigators are participating in several trials.

The CABERNET trial evaluated the NexStent (EndoTex, Cupertino, CA) carotid artery stent in conjunction with the FilterWire (Boston Scientific Corporation, Natick, MA) in 443 patients considered at high risk for endarterectomy. Device placement was successful in 99.1% of attempts with the FilterWire, and in 96.9% of stent placement attempts. Endpoint results, which included all death, stroke, and MI, were 0.5%, 3.4%, and 0.2%, respectively, for a composite rate of 3.8%.

The MAVErIC trials evaluated the use of the Exponent stent and the GuardWire temporary occlusion system (Medtronic, Inc., Santa Rosa, CA) in treating carotid artery stenosis. Procedural success was reported in 85.9% of the 99 patients included in the MAVErIC I (feasibility) phase, and in 90.1% of the 399 MAVErIC II patients (88.2% overall). Composite 30-day MACE rates over the two trials were 5.2% (death, 1%; stroke, 3.6%; and MI, 1.8%). The rate of target vessel revascularization in MAVErIC I at 1 year was 2%.

Guidant Receives FDA Approval for Its Carotid Stent System
August 31, 2004—Guidant Corporation (Indianapolis, IN) announced earlier today that it has received FDA approval for its carotid stent system, which is composed of the RX Acculink Carotid Stent System and the RX Accunet Embolic Protection System. The approval is the first the FDA has granted for carotid artery stenting (CAS) and embolic protection technology in the US. The FDA states that the devices were approved for use in patients who have had symptoms of a stroke or who have a carotid artery blockage of at least 80%, and who are not good candidates for endarterectomy.

The approval was given based on a review of the three ARCHeR trials, the 1-year composite endpoint results of which were presented at this year's Vascular Annual Meeting by Ronald M. Fairman, MD, Chief of Vascular Surgery at the University of Pennsylvania. The ARCHeR trials enrolled a total of 581 patients considered at high risk for carotid surgical procedures at 48 sites. ARCHeR 1 used the Acculink stent without an embolic protection device; ARCHeR 2 incorporated the Accunet, and ARCHeR 3, which was primarily a 30-day test of the delivery system, used the Rx Accunet. Inclusion and exclusion criteria were the same for each phase of the trial. Eligible patients were either symptomatic (greater than 50% stenosis) or asymptomatic (greater than 80% stenosis).

Neurologic outcomes were evaluated by independent neurologist