European ICSS Study Concludes CAS Not as Effective as CEA in the Short-Term
February 25, 2010—Findings from the International Carotid Stenting Study (ICSS) suggest that in the short-term, carotid artery stenting (CAS) was neither as safe nor as effective at preventing stroke as carotid endarterectomy (CEA). The Lancet and The Lancet Neurology published the ICSS study and a substudy, respectively, online ahead of print that concluded that CEA is safer than CAS as a treatment for carotid blockages that can lead to stroke. Detailed abstracts of the studies are available at the above links to the journals’ Web pages.
The studies showed that CEA reduces the risk of stroke and death approximately in half within 30 days of treatment compared to stenting and significantly reduces the risk of stroke, death, and treatment-related myocardial infarction (MI) in the first few months after diagnosis. ICSS was funded by the United Kingdom’s Medical Research Council, the Stroke Association, the European Union, and Sanofi-Synthélabo (now Sanofi-Aventis, Paris, France). Professor Martin M. Brown, MD, was the chief investigator of ICSS.
The ICSS investigators assessed the effectiveness of CAS and CEA for preventing stroke, death, and procedure-related MI in 1,713 patients with recently symptomatic carotid stenoses. Patients were randomly assigned to stenting (n = 855) or surgery (n = 858) and were followed for up to 120 days after randomization.
The investigators reported that patients in the stent group had a significantly greater risk of stroke, death, or procedure-related MI within 120 days of randomization—the absolute risk was 8.5% compared with 5.2% in the surgery group. Additionally, within 30 days of treatment, the rate of stroke or death in the stent group was nearly twice the rate recorded in the surgery group. This difference was mainly due to a higher number of nondisabling strokes recorded in the stent group (36 vs 11 within 30 days of treatment), whereas the number of disabling strokes or deaths did not differ significantly (26 vs 18).
The ICSS investigators concluded, "Completion of long-term follow-up is needed to establish the efficacy of treatment with CAS compared to CEA. In the meantime, CEA should remain the treatment of choice for symptomatic patients suitable for surgery."
The Lancet noted that because investigators who assessed patients during follow-up were not blinded to treatment allocation, there was the possibility of ascertainment bias that might explain the higher incidence of nondisabling strokes found in the stent group. Therefore, in a substudy of ICSS published in The Lancet Neurology, Leo Bonati, MD, et al conducted a blinded analysis of the ICSS trial to assess the rate of ischemic brain injury on magnetic resonance imaging (MRI) after treatment in the two groups. Of the 50 centers in ICSS, seven took part in the MRI substudy, which included 124 CAS patients and 107 CEA patients.
Three times as many patients in the CAS group had new ischemic lesions on diffusion-weighted imaging on posttreatment scans than in the CEA group; therefore, the investigators concluded that the difference in clinical stroke risk in ICSS is unlikely to have been caused by ascertainment bias. Protection devices did not seem to be effective in preventing cerebral ischemia during stenting. Diffusion-weighted imaging might serve as a surrogate outcome measure in future trials of carotid interventions.
The ICSS MRI investigators stated that these neuroimaging data confirm that CEA is safer than CAS and that the increased risk of nondisabling stroke after stent treatment is unlikely to have been caused by ascertainment bias. Most of the new ischemic lesions were not associated with symptoms of stroke at the time of stenting, and the investigators suggest that the most likely explanation is that particles of atheromatous plaque are released during implantation of the stent, which are too small to cause any noticeable symptoms at the time, but nevertheless lead to small areas of brain damage.
Leading carotid interventionists discussed the contrasting findings from CREST and ICSS with Endovascular Today. According to interventional radiologist Barry T. Katzen, MD, who is a CREST investigator, one of the major differences between CREST and ICSS was the training and qualification of the interventional operators. "CAS is an operator- and learning curve-dependent procedure, which was demonstrated in the difference in outcomes between the two trials. The CREST qualification process was rigorous and outcomes based, with many operators being excluded and others being required to increase their experience and demonstrate proven low morbidity before being accepted as randomizing physicians. Additionally, only 72% of patients with CAS in ICSS had embolic protection. Clearly, less experienced operators performing CAS with low rates of embolic protection will produce outcomes that are poorer than those produced in CREST, which had the lowest event rates in both arms of any published trials. European sites should have a greater emphasis on training and experience." Dr. Katzen is co-chief medical editor of Endovascular Today.
Interventional cardiologist Christopher J. White, MD, noted that both CREST and ICSS showed no differences for their primary endpoints between surgery and stenting. In more than 800 patients, ICSS surgeons reported 0.5% MI, whereas CREST surgeons reported 2.3% MI in more 1,200 patients. These data suggest that ICSS does have an ascertainment bias, Dr. White stated to Endovascular Today.
Furthermore, ICSS considered interventionists to be experienced if they had placed a total of 10 carotid stents in their careers, whereas surgeons were required to have done 50 operations. Dr. White pointed out that two inexperienced interventionists who were being tutored caused five major strokes in 11 patients, which were counted in the final tally. By contrast, three-fourths of CREST investigators qualified for that study through a roll-in program that made sure that learning curve issues had been dealt with.
"At the end of the day, both ICSS and CREST support clinical equipoise between surgery and stenting," concluded Dr. White. "Patients and their doctors should make informed decisions about whether a stent or surgery is best for them."
Interventional neurosurgeon L. Nelson Hopkins, MD, a CREST investigator, stated that although ICSS was well run by experienced investigators, credentialing was significantly less rigorous in ICSS than in CREST. Dr. Hopkins also observed that embolic protection was only recommended and used in 72% of procedures in ICSS compared with CREST, which mandated embolic protection with forced lead-in experience.
"CREST shows that CAS has reached parity with CEA, that the two procedures are complimentary, and that further study of the CREST data set will suggest how to improve patient selection," concluded Dr. Hopkins. "So hopefully, the Centers for Medicare & Medicaid Services will give us the opportunity to offer both procedures."
NovoStent’s Samba Receives CE Mark to Treat SFA and Popliteal Disease
March 1, 2010—NovoStent Corporation (Mountain View, CA) announced that it has received CE Mark approval for its Samba stent and delivery system for treating peripheral arterial disease. The Samba stent was designed to treat the highly varied presentation of atherosclerotic disease in the superficial femoral and popliteal arteries.
According to the company, CE Mark approval was supported by data from NovoStent’s SAMBA trial that enrolled patients in Germany in 2009. Michael Dake, MD, presented partial 6-month results of the SAMBA trial at the International Symposium on Endovascular Therapy, which convened in Hollywood, Florida on January 17-21. Lesions treated in the trial included a wide spectrum of disease, such as total occlusions, eccentric calcified plaque, ulcerating lesions, and thrombotic occlusions. Also included in the trial were several isolated popliteal lesions, in which interventionists typically avoid placing stents because of the possibility of stent fracture.
NovoStent features a self-expanding alternating helix technology that provides over 50% vessel coverage. The company stated that because of the absence of axial connectors and its flexible design, there have been no instances of stent fracture in any of the company’s preclinical or clinical trials. NovoStent’s stents employ an ultrathin helical macro structure to provide flexibility and radial strength and a microcell structure that can be tailored for different vascular anatomies, the company stated.
SLEUTH Shows Benefit of Ekos’s Ultrasound Therapy to Treat Brain Hemorrhage
February 25, 2010—Ekos Corporation (Bothell, WA) announced that David W. Newell, MD, presented findings from the SLEUTH (Safety of Lysis With Ultrasound in the Treatment of Intracerebral [ICH] and Intraventricular Hemorrhage [IVH]) study at the International Stroke Conference in San Antonio, Texas. Dr. Newell is Co-Executive Director of the Swedish Neuroscience Institute in Seattle, Washington, which conducted SLEUTH. Ekos noted that ICH is a devastating form of stroke in which half of all patients die within 1 month of the event and those who survive typically experience dramatic loss of brain function and motor skills.
According to Dr. Newell, the objective of SLEUTH was to evaluate the safety and efficacy of a novel therapy that combines ultrasound with recombinant tissue plasminogen activator (rt-PA) delivered through a microcatheter directly into spontaneous IVH or ICH patients, to facilitate evacuation of the hemorrhage. Thirty-five patients presented at the Swedish Neuroscience Institute with ICH and IVH and were screened between November 2008 and July 2009 for entry into the study. Entry criteria included the spontaneous onset of ICH ≥ 25 mL and or IVH producing ventricular obstruction. Nine patients (aged 38–83 years, average = 63; 6 men, 3 women) who met entry criteria were consented and entered into the trial. A ventricular drainage catheter and an ultrasound microcatheter were stereotactically delivered together directly into the IVH or ICH. The patients were treated with rt-PA and 24 hours of continuous ultrasound, and gravity drainage was performed. In patients with IVH, a total of 3 mg of rt-PA was injected, and in patients with intraparenchymal hemorrhages, a total of 0.9 mg of rt-PA was injected in three doses over 24 hours.
Dr. Newell reported that all patients had significant volume reductions of the treated hemorrhage. The mean percentage volume reduction after 24 hours of treatment, compared to the pretreatment stability scans, as determined by computed tomography were 59% ± 5% for ICH and 45.1% ± 13% for IVH (one ICH patient was excluded from analysis because of catheter breakage). There were no intracranial infections and no significant episodes of rebleeding by clinical or computed tomography assessment. There was one death by 30 days after admission. Clinical improvements, as determined by a decrease in the National Institutes of Health Stroke Score, were demonstrated at 30 days in seven of nine patients. The rate of thrombolysis was compared between eight patients who completed treatment to cohorts of patients treated using identical doses of tPA and catheter drainage without ultrasound for IVH and ICH (courtesy of MISTIE and CLEAR studies, which are large IVH/ICH studies sponsored by the National Institutes of Health that are already underway and do not use ultrasound acceleration). Compared to MISTIE and CLEAR data, SLEUTH investigators observed a faster rate of lysis during the first 24 hours of treatment for IVH (P = .046) and for ICH (P = .074) in the patients treated with sonolysis plus tPA.
"Lysis and drainage of spontaneous ICH and IVH with reduction of mass effect can be accomplished rapidly and safely by sonothrombolysis using stereotactically delivered drainage and ultrasound catheters through a burr hole," commented Dr. Newell. "A larger clinical trial with catheters specifically designed for brain blood clot removal is warranted."
Dr. Newell concluded, "The fastest, safest, and most complete way to remove a clot can make a difference between life and death. Ekos’s new therapy has clearly shown promising results, and we are excited to learn more."
Study Supports Endovascular Stenting for Vertebral Artery Stenosis
February 9, 2010—In the Journal of the American College of Cardiology,Stephen Jenkins, MD, et al published findings from a study that sought to evaluate the safety and long-term durability of catheter-based therapy for symptomatic vertebral artery stenosis (VAS) (2010;55:538–542).
According to the investigators, symptomatic VAS carries with it a 5-year 30% to 35% risk of stroke. The 2-year mortality approaches 30% for medically managed strokes involving the posterior circulation. Surgical bypass is rarely performed because of high morbidity and mortality. Therefore, endovascular revascularization with primary stenting offers an attractive treatment option for these patients.
In the study, 105 consecutive symptomatic patients (112 arteries, 71% men) underwent stent placement for extracranial (91%) and intracranial (9%) VAS from 1995 to 2006. Fifty-seven patients (54%) had bilateral VAS, 71 patients (68%) had concomitant carotid disease, and 43 patients (41%) had a previous stroke.
As reported by the investigators, procedural and clinical success was achieved in 105 (100%) and 95 (90.5%) patients, respectively. One-year follow-up was obtained in 87 patients (82.9%), of which 69 patients (79.3%) remained symptom-free. At 1 year, six patients (5.7%) had died and five patients (5%) had a posterior circulation stroke. Target vessel revascularization occurred in 7.4% at 1 year. At a median follow-up of 29.1 months (interquartile range 12.8–50.9 months), 13.1% underwent target vessel revascularization, 71.4% were alive, and 70.5% remained symptom-free.
The investigators concluded that in experienced hands, stenting for symptomatic VAS can be accomplished with a very high success rate (100%) with few periprocedural complications and is associated with durable symptom resolution in the majority (approximately 80%) of patients. Therefore, endovascular stenting of vertebral artery atherosclerotic disease is safe and effective compared with surgical controls and should be considered first-line therapy for this disease.
Lumen’s FiberNet EPS Shows Success in High-Risk CAS Patients in EPIC Study
March 1, 2010—The Society for Cardiovascular Angiography and Interventions announced that the multicenter EPIC (FiberNet Embolic Protection System [EPS] in Carotid Artery Stenting [CAS] Trial) study found that the FiberNet EPS (Lumen Biomedical, Inc., Maple Grove, MN) had a 97.5% success rate when used in patients undergoing CAS. Subbarao Myla, MD, et al published the findings online ahead of print in Catheterization and Cardiovascular Interventions.
The EPIC investigators evaluated the safety and efficacy of the FiberNet EPS for embolic protection during CAS. The study was designed to demonstrate that the 30-day major adverse event rate of all death, stroke, and myocardial infarction is significantly less than the performance goal of 8.3% from the ARCHER 3 results published by William A. Gray, MD, et al in the Journal of Vascular Surgery (2006;44:258–268).
The EPIC trial enrolled 237 patients with a mean age of 74 years from 26 centers across the United States and Europe. Study participants were 64% men and 20% had symptomatic carotid artery disease (CAD). Results indicate the combined major adverse event rate at 30 days after carotid endarterectomy for all death, stroke, and heart attack was 3%. Dr. Myla stated that that rate is encouraging. The EPIC investigators concluded that the FiberNet EPS, when used with commercially available stents, produced low stroke rates after CAS in high-surgical risk patients with CAD.
Describing the EPIC investigators’ experience with the FiberNet device, Dr. Myla commented, "The low crossing profile and integration of a primary guidewire shortened procedure time and facilitated lesion crossing and filter placement, especially in the presence of tortuous anatomy. The 0.014-inch guidewire tip demonstrated good torque response, and the guidewire provided excellent support. It was ideal for procedures in which tortuosity would preclude placement of a more structured distal protection device with a stiff delivery catheter. Conformability of the expanded fiber network to the vessel wall and the short landing zone of the device made it ideal for challenging anatomy distal to the lesion. Anecdotally, investigators have commented the FiberNet EPS resulted in fewer vessel spasms."
Prognosis of Patients With PAD Shown to Differ by Disease Localization
February 22, 2010—In the Journal of the American College of Cardiology, Victor Aboyans, MD, et al published finding from a single-center study that sought to assess the general prognosis of patients with peripheral arterial disease (PAD) according to the disease localization (2010;55:898–903). The background of the study is the understanding that PAD is associated with poor cardiovascular disease prognosis; however, it is unknown whether the general prognosis could differ according to PAD topography.
In the study, the investigators reviewed data for all patients who underwent an initial digital subtraction angiography of their lower limbs between January 2000 and December 2005 at the investigator’s hospital. Arterial stenoses ≥ 50% were located by two experienced vascular physicians. The events recorded until April 2007 were death, nonfatal myocardial infarction or stroke, and coronary or carotid revascularization. The primary outcome combined all these events.
The investigators studied 400 PAD patients (aged 68.3 ± 12.3 years; 77.5% men). They noted aortoiliac disease (proximal PAD) and infrailiac disease (distal PAD) in 211 (52.8%) and 344 (86%) cases, respectively. Male sex and smoking were more prevalent in proximal PAD, whereas older age, diabetes, hypertension, and renal failure were more prevalent in distal PAD (P < .05). During the follow-up period (34 ± 23 months), the event-free survival curves differed according to the PAD localization (P < .03). Adjusted for age, sex, cardiovascular disease history and cardiovascular disease risk factors, critical leg ischemia status, and treatments, proximal PAD was significantly associated with a worse prognosis (primary outcome hazard ratio, 3.28; death hazard ratio, 3.18; P < .002 versus distal PAD).
This study is the first to report a poorer general prognosis of patients with proximal (aortoiliac) PAD compared with those with more distal PAD, independent of risk factors and comorbidities, the investigators concluded.
Meta-Analysis Reviews Comparative Studies of TEVAR and Open Surgery
March 1, 2010—Findings from a study that sought to determine whether thoracic endovascular aortic repair (TEVAR) reduces death and morbidity compared with open surgical repair for descending thoracic aortic disease were published by Davy Cheng, MD, et al in the Journal of the American College of Cardiology (2010;55:986–1001). The investigators noted that the role of TEVAR versus open surgery remains unclear. Metaregression can be used to maximally inform adoption of new technologies by utilizing evidence from existing trials. This was the background of the study.
In the study, data from comparative studies of TEVAR versus open repair of the descending aorta were combined through meta-analysis. Metaregression was performed to account for baseline risk factor imbalances, study design, and thoracic pathology. Due to significant heterogeneity, registry data were analyzed separately from comparative studies. The analysis included 42 nonrandomized studies involving 5,888 patients (38 comparative studies, four registries). Patient characteristics were balanced except for age, as TEVAR patients were usually older than open surgery patients (P = .001). Registry data suggested overall perioperative complications were reduced.
The investigators reported that in the comparative studies, all-cause mortality at 30 days (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.33–0.59) and paraplegia (OR, 0.42; 95% CI, 0.28–0.63) were reduced for TEVAR versus open surgery. In addition, cardiac complications, transfusions, reoperation for bleeding, renal dysfunction, pneumonia, and length of stay were reduced. There was no significant difference in stroke, myocardial infarction, aortic reintervention, and mortality beyond 1 year. Metaregression to adjust for age imbalance, study design, and pathology did not materially change the results.
The investigators concluded that current data from nonrandomized studies suggest that TEVAR may reduce early death, paraplegia, renal insufficiency, transfusions, reoperation for bleeding, cardiac complications, pneumonia, and length of stay compared with open surgery. They advised that sustained benefits on survival have not been proven.
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