Endovascular Carotid Stenting To: Joseph G. Cacchione, MD, FACC From: Mark H. Wholey, MD Date: April 21, 2003 Thank you for the invitation to participate in forwarding comments on the status of endovascular carotid stenting as an alternative to the surgical procedure, carotid endarterectomy. Carotid stenting is now being done in essentially all of the trials utilizing a distal protection filter device. The filter device is designed to capture any embolic debris that might occur during the procedure. At the completion of the stenting procedure, when the vessel is restored to normal dimensions, the filter is removed. Analyses of the filter, and its contents, have demonstrated a macrocopic and/or microscopic particulate material in 30-50%. This has had a dramatic effect on the stroke incidence. In the single institution studies, as well as the World registry in those procedures done without a distal protection filter device, the periprocedural stroke and death rate was approximately 5%. This was reduced to 3% in the symptomatic population, and from 3.5 to 1.6% in the asymptomatic subset. The World registry represented 41 sites in the US and Europe, as well as our own Pittsburgh Vascular Institute as a part of UPMC-Shadyside also report favorable data with periprocedural stroke and death in the 3.5% range. In the last 122 patients with distal protection, our periprocedural stroke and death was 1.6%. All patients in the UPMC Shadyside, Pittsburgh Vascular Institute experience had neurologic assessment with a neurologist pre-procedure evaluation, as well as follow-up at discharge, 30 days, 6 months, 1 year and annually thereafter. Considering that these patients represented a high-risk subset, we are quite pleased with these results. They certainly appear better than the surgical literature, and in fact, were equivalent or better than the NASCET and the ACAS trials, both of which represented low risk trials. NASCET was a symptomatic trial, with very restricted entry criteria and essentially no high-risk enrollments other than the indication of contralateral occlusion. There is, however, the continuing question that single institution studies whether surgical or endovascular stenting, always report lower data that the carefully controlled, monitored trials. The first significant randomized clinical trial comparing carotid stenting with distal protection versus carotid endarterectomy was reported at the AHA in November 2002. This SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) trial was an industry sponsored randomized clinical trial enrolling 400 patients in the registry and 307 patients in the randomized component. The surgical endarterectomy arm of the randomized trial had a startling 12.6% periprocedural stroke, death, and MI event rate at 30 days. The stenting arm had a 5.6%, stroke, death and MI incidence rate. Stenting in all parameters of the SAPPHIRE trial had more favorable outcomes than surgery. I was on the executive committee for that particular trial and the results were quite startling when we compared the incidence of myocardial infarction both q-wave and non-q-wave in the surgical arm of almost 7%. Furthermore, 5% of the patients had cranial nerve palsy secondary to the endarterectomy procedure. The next most significant trial was the ARCHeR (ACCULINK™ for Revascularization of Carotids in High Risk Patients) trial that I reported on the American College of Cardiology meeting in March 2003. This trial also reported a 6% periprocedural stroke, death and MI rate as compared to the historical surgical control of the high risk subset of patients of 10-12% periprocedural stroke, death and MI rate. The ARCHeR trial also reported that of the 513 patients enrolled, of which 437 were included in the registry, 140 patients had restenosis of significant degree greater than 80% from prior surgical endarterectomy. Those patients, when stented, had an increase of only 0.7% stroke and 1.4% incidence of stroke, death and MI. Both of these trials enrolled only high surgical risk subset patients. In the ARCHeR trial, the periprocedural stroke rate was actually 4% with most of the strokes being minor and returning to baseline within 30 days. 3.4 % of the patients had minor strokes and 1.6% had major strokes. This is also in contrast with the surgical literature, whereby most of the strokes occurring following endarterectomy are major strikes. At the present time, the consensus of opinion is that surgical endarterectomy is as good as it will get. In the meantime, carotid stenting with distal protection devices are in their first generation and the data in the high-risk subsets is clearly better than surgery at this point in time. The NASCET data of 5.6% periprocedural stroke and death, again, represented a low risk trial, and presently when we analyze the data from the two currently completed trials, it would appear that the high risk surgical subset patients with periprocedural stroke and death is the equivalent of the low risk NASCET data. In essence, we have a new order, and it could well be that carotid stenting represents the gold standard, at least for these patients considered high risk. The results of SAPPHIRE and ARCHeR trials are what most of the investigators have anticipated, and it is very likely that the additional trials, to include MAVErlC (Evaluation of the Medtronic AVE Self-expanding Carotid Stent System with Distal Protection In the Treatment of Carotid Stenosis), BEACH (Boston Scientific EPI – A carotid stenting trial for High Risk Surgical Patients), CABERNET (Carotid Artery Revascularization Using the Boston Scientific EPI Filterwire ™ and The EndoTex ™ Nexstent ™), and SECURITY (A Registry Study to Evaluate the Neuroshiled Bare Wire Cerebral Protection System and X.act Stent in Patients at High Risk for Carotid Endarterterectomy) will complete enrollment within this year, and most likely will report all event rates within the 5% category. Again, these are all high surgical risk patients with well-defined risk criteria, and to date there has never been a single surgical trial of a high-risk nature. Most of these patients being enrolled are either non-surgical candidates or at excessive risk for endarterectomy. Unfortunately, in all of these trials there are certain patients who do not meet the entry criteria. Furthermore, they are also not candidates for endarterectomy. This would include patients with significant vertebrobasilar lesions or internal carotid lesions at the base of the skull that are clearly not surgically accessible. Since those patients who did not fit the trial, were not service covered admissions, and with the resistance from Medicare and the insurer to cover those costs, we frequently had to send those patients home, and basically assign them a stroke or death warrant. We clearly need an expedited review to allow these patients, especially the high surgical risk category, or those patients who simply refuse surgery, to come under a service covered admission and allow at least hospital reimbursement. Mark H. Wholey, MD, Chairman Pittsburgh Vascular Institute 412-623-2083 wholeymh@msx.upmc.edu