Results from several trials released at the TransCatheter Therapeutic (TCT) meeting, in Washington DC, have demonstrated carotid artery stenting is fast becoming the treatment of choice for a variety of clinicians. Not only did the results highlight the durability of carotid stenting vs carotid endarterectomy and show the benefits of embolic protection devices, but also that carotid stenting can be utilized safely in real-world clinical settings with physicians of varying levels of experience.
Preliminary three-year data from the Stenting and Angioplasty with Protection in Patients at HIgh Risk for Endarterectomy (SAPPHIRE) and final three-year data from the US Carotid Feasibility Study (USFS) presented at the 2005 Transcatheter Cardiovascular Therapeutics meeting, demonstrate the long-term durability of carotid artery stenting for the prevention of stroke versus carotid endarterectomy in high-risk surgical patients.
Dr Jay S Yadav, from the Cleveland Clinic Foundation and a principal investigator for the SAPPHIRE trial and USFS, commented “these results are extremely important data and show the long-term durability of carotid stenting in this patient population.” He added that the percutaneous approach was more durable than the surgical.
A total of 334 patients in the SAPPHIRE trial were randomized to either carotid stenting or surgery. Patients who received carotid stenting with the Precise Nitinol Self-Expanding Stent and Angioguard XP Emboli Capture Guidewire System maintained a low incidence of stroke after the first 30-days for the duration of the three-year follow-up in the USFS and SAPPHIRE. In the SAPPHIRE trial, at 36 months the incidence of stroke was virtually identical for both carotid stenting and surgery (7.1% for carotid stenting and 6.7% for surgery, P = 0.945). The three-year incidence of stroke across the randomized and non-randomized carotid stenting treatment groups in SAPPHIRE and the USFS had only an average increase of 4.0% over the 30-day stroke rate.
An analysis of target lesion revascularization (TLR) with follow up to three years in the randomized arms of SAPPHIRE, showed re-intervention rates of 3.0% for carotid stenting and 7.1% for CEA, P = 0.084. Three-year TLR rates for carotid stenting were similar in the USFS.
Moreover, Yadav said that implications of the trial results were that questions over the durability of carotid stenting vs carotid endarterectom have been answered, as the overall risk of stroke drops by 1% per year following carotid stenting. In addition, Yadav said that asymptomatic patients “faired extremely well.”
Data from the SAPPHIRE, USFS, and CASCADE clinical trials were also presented in two poster sessions highlighting carotid stenting involving Angiogaurd. The data suggests emboli protection is effective in preventing major strokes during carotid stenting. 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 Angioguard. In addition, 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 these trials resolved with time. Both trials were sponsored by Cordis, a Johnson & Johnson company.
Separately, Yadav also announced preliminary results from a study of carotid artery stenting in high-risk patients, Carotid AccuLink/AccuNet Post Approval Trial to Uncover Rare Events (CAPTURE). CAPTURE is an FDA-required post-approval study designed to determine whether carotid stenting can be performed safely in ‘real-world’ settings with physicians of differing levels of experience and to evaluate the effectiveness of Guidant’s training program.
Results were based on data from 1,603 patients receiving Guidant’s FDA-approved RX AccuLink Carotid Stent System and RX Accunet Embolic Protection System, which are indicated for high surgical risk patients. Patients in CAPTURE were treated by 240 physicians, including interventional cardiologists, interventional radiologists, interventional neuroradiologists, vascular surgeons and neurosurgeons, at 118 hospitals in the US. CAPTURE has enrolled more than 2,800 patients to date and continues to recruit patients.
The initial results of the study confirm positive earlier data on carotid stenting for high-risk patients. In addition, the study suggests that the procedure can be performed safely by physicians of different experience levels. The rate of death, stroke and myocardial infarction within 30-days of the procedure was 5.1%.
“CAPTURE is a landmark study. 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.” said Yadav. “The excellent results and the overall ease of use of the system make this a breakthrough treatment for stroke prevention in high-risk patients,” concluded.
In addition to the CAPTURE trial, Guidant is participating in the CREST trial evaluating carotid artery stenting in low-surgical risk patients, which continues to enrol patients.
Results from the BEACH clinical trial, which was designed to evaluate the benefits of carotid stenting in conjunction with embolic protection for the treatment of carotid artery disease, demonstrated improved blood flow within the vessel and the vessel remained open up to one year post-procedure in patients at high risk for carotid endarterectomy.
The study utilized Boston Scientific’s Carotid Wallstent Monorail Endoprosthesis, used in combination with the company’s FilterWire EX and FilterWire EZ Embolic Protection Systems. Dr Michael R Jaff, Assistant Professor of Medicine at Harvard Medical School and Medical Director of the Vascular Ultrasound Core Laboratory, Massachusetts General Hospital, said that the data showed carotid stenting using the Carotid Wallstent Endoprosthesis and FilterWire System may offer a safe and durable treatment strategy in high-risk patients with carotid artery disease.
BEACH is a prospective, non-randomized, single-arm clinical trial that enrolled 747 patients at 47 US sites, with 480 patients in the pivotal phase of the trial. The trial has a composite primary endpoint of cumulative mortality and morbidity through one year, consisting of stroke, death and myocardial infarction. All patients underwent carotid duplex ultrasonography (CDUS) before, immediately after and at one, six and 12 months after carotid stenting. As previously disclosed, cumulative mortality and morbidity were 5.6% at 30 days and 9.1% at one year.
According to data in this analysis, blood velocity in the carotid artery was reduced by more than half during the pumping phase of the heart (peak systolic velocity) up to a year after implantation. The device also reduced blood velocity in the carotid artery nearly three-fold during the relaxation phase of the heart (end diastolic velocity) up to a year after implantation. Although velocity measurements at 12 months were statistically greater than those observed immediately post-procedure, there were no clinically relevant changes in stent patency and there was no increase in neurological events or need for repeat intervention. In addition, improvements in blood flow were stable between six and 12 months.
According to an additional analysis, significant resources were used in providing interventional treatments to patients with carotid artery stenosis. These patients were hospitalized for a median of two days overall and the two symptomatic subgroups experienced longer procedure times. The resource use associated with these types of cases would not be appropriately addressed by Medicare payments. Under the Centers for Medicare and Medicaid Services National Coverage Decision for carotid stenting, symptomatic patients at high risk for carotid endarterectomy and with carotid artery stenosis of >=70 percent are covered for approved carotid stenting devices implanted at a credentialed facility.
Jaff and colleagues analyzed all of the duplex ultrasound studies performed in the BEACH trial. “These results show not only that the devices improve blood flow through one year in most patients, but also that the performance of the stent can be safely and accurately analyzed by ultrasonography, a non-invasive technique in a multi-center prospective registry,” he commented.
Carotid Wallstent Monorail Endoprosthesis and FilterWire EX/EZ Embolic Protection Systems have not been cleared in the US.
In addition, results were also presented from the Carotid Artery Revascularization Using the Boston Scientific EPI FilterWire EX/EZ and the EndoTex NexStent (CABERNET) trial. The CABERNET trial was designed to evaluate the safety and efficacy of carotid artery stenting as a minimally invasive alternative for treating carotid artery disease and reducing the risk of stroke in patients either ineligible or at high risk for surgery. This prospective, non-randomized, multi-center, single-arm clinical study enrolled a total of 454 patients, at 19 clinical sites (15 in the US and four sites outside of the US).
The composite major adverse event rate at one-year, defined as any death, stroke or myocardial infarction, 30 days post-procedure plus any ipsilateral stroke including any death as a result of an ipsilateral stroke from 31 to 365 days was 4.5% (Death 0.5%, Stroke 4.0%, MI 0.2%).
Dr L Nelson Hopkins, Professor & Chairman of Neurosurgery at the University at Buffalo, State University of New York, said that the results compare very favorably with other similar US high risk carotid stenting trials and appear competitive with the major carotid endarterectomy trials.
In a discussion following the presentation of the SAPPHIRE and CABERNET trials, Hopkins said, “What we must realize is that our understanding of the carotids is improving, but so are our skills and techniques.”