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Carotid Angioplasty
conduct of a trial for any use not covered in the labeling does require an IDE. Studies of vascular stents in the carotid arteries, therefore, require an FDA-approved IDE as this use is not mentioned in the labeling and this use is considered a significant risk.
3:30 pm Carotid Angioplasty Donald E. Schwarten, MD
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PERCUTANEOUS transluminal angioplasty (PTA) is an accepted technique for treating vascular occlusive disease in most territories, except cerebrovascular circulation, where concerns about the risks of procedure-related embolization to the central nervous system have limited the use of angioplasty. In addition, the results of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) made it clear that surgical reconstruction of carotid bifurcation is the treatment of choice for patients with greater than 75% stenoses in the presence of symptoms. In most institutions where morbidity and mortality meet or surpass that of NASCET, and patients are often discharged after operative intervention in less than 24 hours and can expect a low risk of recurrent disease and perhaps, most importantly, a low risk of subsequent neurologic events. With such good results associated with carotid endarterectomy, is there a place for carotid bifurcation angioplasty with or without stent placement? A review of the literature suggests that concerns about cerebral embolization during carotid angioplasty may be exaggerated (1). In a combined experience of over 300 procedures reported by Tsai, Higashida and Mathias, there was only one clinically significant embolic stroke. In a review of 2,000 brachiocephalic angioplasty procedures that included 523 carotid angioplasties, 2.1% of the procedures resulted in morbidity (2). Theron has reported that when he performed carotid bifurcation angioplasty without a second "cerebral protection balloon" that 9% of patients sustained a clinically significant neurologic event (3). When he employed this second distal balloon, there were no embolic events. What is not possible to ascertain from Theron's report is where did the patients who sustained embolic complications reside in series' sequence. Were they among the first patients and therefore on the beginning of the learning curve? No embolic episodes occurred during carotid angioplasty in patients emolled in the North American Cerebral PTA Register. All patients were subjected to a rigorous neurologic examination by a qualified neurologist and underwent cross-sectional imaging studies of the brain both before and after angioplasty. None of the angioplasty series has been randomized. Selection bias is likely to have influenced many of the series and they can certainly not be considered comparable to the NASCET Trial. The angioplasty series report acceptable technical success rates, and probably acceptable morbidity and mortality rates. But, they lack followup data related to protection of a patient from future
neurologic events and restenosis, although the restenosis rate will probably be low and may not be significant. Endarterectomy eliminates the plaque with its associated ulcerations and restores normal lUminal caliber. It is associated with a risk of recurrent stenoses with reported ranges of 6% to 32%, and it has been observed that these recurrent stenosis behave differently from the native lesions (4). The assumption is that the restenosis is a smooth, intimal hyperplastic lesion that is much less thrombogenic than native atherosclerotic lesions. Neurologic symptoms are uncommon after carotid endarterectomy with symptomatic recurrent stenoses occurring in less than 5% of cases. Under the guidelines of the North American Cerebral PTA Register, patients with carotid bifurcation disease who would qualify for operative intervention under NASCET criteria would be considered candidates for angioplasty if, the vascular surgeon involved in the patient's care assessed the risk of operative intervention as 5% or greater (5). The inclusion criteria, preprocedure work up, intraprocedure guidelines, and postprocedure examinations and follow-up should serve as an ideal model for any register. Every patient who satisfied inclusion criteria and accepted angioplasty was examined by a neurologist. The patient underwent duplex imaging, CT or MR imaging, and had a complete 4-vessel arteriogram before the procedure. The technical aspects of the procedure were left to the individual interventionalist with relatively broad guidelines. Postprocedure examinations included repeat neurologic examination by the same neurologist, duplex imaging, and brain MR imaging or CT. Subsequent examinations included quarterly duplex studies. A I-year anniversary arteriogram was requested, the last duplex examination and neurologic examination was conducted at 2 years after the procedure. The carotid angioplasty procedure was performed on patients who had been treated for at least the preceding 24 hours with salicylates and were systemically heparinized to an ACT of 300 or greater during the procedure. Atropine was administered just before catheter manipulation within the bulb to prevent severe bradyarrhythmias. With the patient mildly sedated, baseline neurologic examinations were conducted and then, as the procedure was performed, frequent neurologic examinations were made. Some patients were given a trial of intraarterial urokinase when a filling defect was present or there had been a significant change in the angiographic anatomy since the preprocedure diagnostic study. The angioplasty procedure itself was performed with standard 5-F angioplasty catheters using the guidewire exchange technique, as has been described in most carotid angioplasty series. The second occlusion balloons advocated by Kachel and Theron were not employed in this series, nor were stents employed. The results of this series were similar to those reported previously, except that one patient developed an extensive dissection at the angioplasty site, which could have been salvaged with a stent had an appropriate stent been
available. This patient experienced a right hemispheric stroke. Stents are now being employed at the carotid bifurcation and there are a number of advocates of stentsupported carotid bifurcation angioplasty. Regulatory resistance to this procedure is strong in the United States. A limited number of relatively large series have been reported. Roubin (6) has used Palmaz stents, Wall stents, and Gianturco-Roubin II stents for stent-supported angioplasty at the carotid bifurcation. He has reported on more than 207 vessels with a major stroke incidence of 1.3% (one contralateral stroke from a cardiogenic embolus) and seven minor strokes (4.6%), all of whom recovered to preprocedure neurologic baseline within 48 hours. There was one death in this series secondary to a retroperitoneal bleed. Among the Wall stent patients, there was no restenosis greater than 60% and in the series of patients treated with a Palmaz stent, 12.3% of the patients exhibited stent deformity at the time of 6-month angiographic follow-up. Only one patient in this series exhibited recurrent transient ischemic attacks during the follow-up period. That patient had a cardiomyopathy and the transient ischemic attacks occurred in multiple different anterior and posterior circulation territories. Follow-up angiography associated with the transient ischemic attacks consistently revealed a widely patent stent site. The authors purportedly point out that the devices used to stent the extracranial carotid arteries were not designed specifically for this purpose. The ideal stent for a carotid bifurcation may be under development and we, therefore, need to be very careful not to push the envelope and invalidate a procedure that indeed may be a viable alternative to carotid endarterectomy. Other reports of carotid stent placement are being reviewed. More than 500 patients underwent the carotid stent placement procedure at seven different centers, and preliminarily, it appears that the results will be similar to those achieved at the University of Alabama. Ideally, a large multicenter prospective registry should be developed. Then, if the data accumulated from the registn! are acceptable, a large multicenter prospective randomized trial to compare endarterectomy with carotid artery stent placement would follow. In Europe, there is a large ongoing multicenter trial on percutaneous carotid intervention and it appears likely that regulatory agencies in the United States will support a prosective randomized trial of stenting vs. endarterectomy, leap frogging the multicenter registry.
Selected Bibliography 1. Ferguson RGD, Lee LI, Connors JJ, et al. Angioplasty of the extracranial and intracranial vasculature. Semin Intervent Radiol 1944; 11:64. 2. Kachel R, Enbert G. Basche, et al. Percutaneous transluminal angioplasty (dilatation) of carotid, vertebral and innominate artery stenosis. Cardiovasc. Intervent Radiol. 1987; 110:142-146.
3. Theron J, Courtheoux P, Henriet JP, Pelouz G, Der10nJM, Maiza D. Angioplasty of supra-aortic arteries. J Neuroradiol 1984; 11:187-200. 4. Strandness DE Jr. Surgical Therapy for Extracranial Arterial Disease in Vascular Diseases Surgical and Interventional Therapy. Strandness DE, Jr., VanBreeda A, eds. Churchill Livingstone, New York, NY, 1994. 5. The North American Cerebral Percutaneous Transluminal Angioplasty Register (NACPTAR) Investigated Update of the Immediate Angiographic Results and In-Hospital Central Nervous System Complicationss of Cerebral Percutaneous Transluminal Angioplasty. Presented at the American Heart 66th Scientific Session, Anaheim, CA, November 14, 1995. 6. Yadav JS, Roubin GS, Iyer S, et al. Elective Stenting of the Extracranial Carotid Arteries, presented at the 7th Annual Symposium on Vascular Innterventions, Birmingham, AL, September 11-13, 1996.
3:50 pm Carotid Stenting: Current Status, Future Prospects Gary S. Roubin, MD, PhD, Jiri Vitek, MD, Sriram Iyer, MD, Jay Yadav, MD, Camillo Gomez, MD Rationale The use of carotid artery stents is a less invasive, potentially safer, and less costly treatment for carotid stenoses. The current standard therapy, carotid endarterectomy, has been shown in randomized trials to be superior to medical management in both symptomatic and asymptomatic patients. However, the translation of these trial results has emphasized the limitations of the surgical approach to the community. The North American Carotid Endarterectomy Surgery Trial (NASCET) was undertaken by a carefully selected group of surgeons and a highly selected subset of patients. The average NASCET site recruited an average of 5 patients per year. Patients with severe cardiopulmonary disorders, the very elderly, and patients with recent strokes were among those not studied in NASCET. To qualify as operators, surgeons had to demonstrate a complication rate of less than 6%. Despite these favorable factors, the perioperative stroke and death rate in NASCET was 6.5%. Recently, a systematic review of a total of 126 studies of endarterectomies concluded that the risk of stroke or death averaged 7.7% in series with neurologic assessment. In the community, Medicare statistics show that the morbidity and mortality is in the range of 10% to 15%. More than 90% of the carotid endarterectomies performed in North America are done under general anesthesia and the average hospital stay is 3 days. Ten percent of patients have cranial nerve palsies; and restenosis after endarterectomy is not uncommon. Finally, an important subset of patients either are at considerably higher risk from endarterectomy or do not have surgery
25
3:30 pm Carotid Angioplasty Donald E. Schwarten, MD
24
PERCUTANEOUS transluminal angioplasty (PTA) is an accepted technique for treating vascular occlusive disease in most territories, except cerebrovascular circulation, where concerns about the risks of procedure-related embolization to the central nervous system have limited the use of angioplasty. In addition, the results of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) made it clear that surgical reconstruction of carotid bifurcation is the treatment of choice for patients with greater than 75% stenoses in the presence of symptoms. In most institutions where morbidity and mortality meet or surpass that of NASCET, and patients are often discharged after operative intervention in less than 24 hours and can expect a low risk of recurrent disease and perhaps, most importantly, a low risk of subsequent neurologic events. With such good results associated with carotid endarterectomy, is there a place for carotid bifurcation angioplasty with or without stent placement? A review of the literature suggests that concerns about cerebral embolization during carotid angioplasty may be exaggerated (1). In a combined experience of over 300 procedures reported by Tsai, Higashida and Mathias, there was only one clinically significant embolic stroke. In a review of 2,000 brachiocephalic angioplasty procedures that included 523 carotid angioplasties, 2.1% of the procedures resulted in morbidity (2). Theron has reported that when he performed carotid bifurcation angioplasty without a second "cerebral protection balloon" that 9% of patients sustained a clinically significant neurologic event (3). When he employed this second distal balloon, there were no embolic events. What is not possible to ascertain from Theron's report is where did the patients who sustained embolic complications reside in series' sequence. Were they among the first patients and therefore on the beginning of the learning curve? No embolic episodes occurred during carotid angioplasty in patients emolled in the North American Cerebral PTA Register. All patients were subjected to a rigorous neurologic examination by a qualified neurologist and underwent cross-sectional imaging studies of the brain both before and after angioplasty. None of the angioplasty series has been randomized. Selection bias is likely to have influenced many of the series and they can certainly not be considered comparable to the NASCET Trial. The angioplasty series report acceptable technical success rates, and probably acceptable morbidity and mortality rates. But, they lack followup data related to protection of a patient from future
neurologic events and restenosis, although the restenosis rate will probably be low and may not be significant. Endarterectomy eliminates the plaque with its associated ulcerations and restores normal lUminal caliber. It is associated with a risk of recurrent stenoses with reported ranges of 6% to 32%, and it has been observed that these recurrent stenosis behave differently from the native lesions (4). The assumption is that the restenosis is a smooth, intimal hyperplastic lesion that is much less thrombogenic than native atherosclerotic lesions. Neurologic symptoms are uncommon after carotid endarterectomy with symptomatic recurrent stenoses occurring in less than 5% of cases. Under the guidelines of the North American Cerebral PTA Register, patients with carotid bifurcation disease who would qualify for operative intervention under NASCET criteria would be considered candidates for angioplasty if, the vascular surgeon involved in the patient's care assessed the risk of operative intervention as 5% or greater (5). The inclusion criteria, preprocedure work up, intraprocedure guidelines, and postprocedure examinations and follow-up should serve as an ideal model for any register. Every patient who satisfied inclusion criteria and accepted angioplasty was examined by a neurologist. The patient underwent duplex imaging, CT or MR imaging, and had a complete 4-vessel arteriogram before the procedure. The technical aspects of the procedure were left to the individual interventionalist with relatively broad guidelines. Postprocedure examinations included repeat neurologic examination by the same neurologist, duplex imaging, and brain MR imaging or CT. Subsequent examinations included quarterly duplex studies. A I-year anniversary arteriogram was requested, the last duplex examination and neurologic examination was conducted at 2 years after the procedure. The carotid angioplasty procedure was performed on patients who had been treated for at least the preceding 24 hours with salicylates and were systemically heparinized to an ACT of 300 or greater during the procedure. Atropine was administered just before catheter manipulation within the bulb to prevent severe bradyarrhythmias. With the patient mildly sedated, baseline neurologic examinations were conducted and then, as the procedure was performed, frequent neurologic examinations were made. Some patients were given a trial of intraarterial urokinase when a filling defect was present or there had been a significant change in the angiographic anatomy since the preprocedure diagnostic study. The angioplasty procedure itself was performed with standard 5-F angioplasty catheters using the guidewire exchange technique, as has been described in most carotid angioplasty series. The second occlusion balloons advocated by Kachel and Theron were not employed in this series, nor were stents employed. The results of this series were similar to those reported previously, except that one patient developed an extensive dissection at the angioplasty site, which could have been salvaged with a stent had an appropriate stent been
available. This patient experienced a right hemispheric stroke. Stents are now being employed at the carotid bifurcation and there are a number of advocates of stentsupported carotid bifurcation angioplasty. Regulatory resistance to this procedure is strong in the United States. A limited number of relatively large series have been reported. Roubin (6) has used Palmaz stents, Wall stents, and Gianturco-Roubin II stents for stent-supported angioplasty at the carotid bifurcation. He has reported on more than 207 vessels with a major stroke incidence of 1.3% (one contralateral stroke from a cardiogenic embolus) and seven minor strokes (4.6%), all of whom recovered to preprocedure neurologic baseline within 48 hours. There was one death in this series secondary to a retroperitoneal bleed. Among the Wall stent patients, there was no restenosis greater than 60% and in the series of patients treated with a Palmaz stent, 12.3% of the patients exhibited stent deformity at the time of 6-month angiographic follow-up. Only one patient in this series exhibited recurrent transient ischemic attacks during the follow-up period. That patient had a cardiomyopathy and the transient ischemic attacks occurred in multiple different anterior and posterior circulation territories. Follow-up angiography associated with the transient ischemic attacks consistently revealed a widely patent stent site. The authors purportedly point out that the devices used to stent the extracranial carotid arteries were not designed specifically for this purpose. The ideal stent for a carotid bifurcation may be under development and we, therefore, need to be very careful not to push the envelope and invalidate a procedure that indeed may be a viable alternative to carotid endarterectomy. Other reports of carotid stent placement are being reviewed. More than 500 patients underwent the carotid stent placement procedure at seven different centers, and preliminarily, it appears that the results will be similar to those achieved at the University of Alabama. Ideally, a large multicenter prospective registry should be developed. Then, if the data accumulated from the registn! are acceptable, a large multicenter prospective randomized trial to compare endarterectomy with carotid artery stent placement would follow. In Europe, there is a large ongoing multicenter trial on percutaneous carotid intervention and it appears likely that regulatory agencies in the United States will support a prosective randomized trial of stenting vs. endarterectomy, leap frogging the multicenter registry.
Selected Bibliography 1. Ferguson RGD, Lee LI, Connors JJ, et al. Angioplasty of the extracranial and intracranial vasculature. Semin Intervent Radiol 1944; 11:64. 2. Kachel R, Enbert G. Basche, et al. Percutaneous transluminal angioplasty (dilatation) of carotid, vertebral and innominate artery stenosis. Cardiovasc. Intervent Radiol. 1987; 110:142-146.
3. Theron J, Courtheoux P, Henriet JP, Pelouz G, Der10nJM, Maiza D. Angioplasty of supra-aortic arteries. J Neuroradiol 1984; 11:187-200. 4. Strandness DE Jr. Surgical Therapy for Extracranial Arterial Disease in Vascular Diseases Surgical and Interventional Therapy. Strandness DE, Jr., VanBreeda A, eds. Churchill Livingstone, New York, NY, 1994. 5. The North American Cerebral Percutaneous Transluminal Angioplasty Register (NACPTAR) Investigated Update of the Immediate Angiographic Results and In-Hospital Central Nervous System Complicationss of Cerebral Percutaneous Transluminal Angioplasty. Presented at the American Heart 66th Scientific Session, Anaheim, CA, November 14, 1995. 6. Yadav JS, Roubin GS, Iyer S, et al. Elective Stenting of the Extracranial Carotid Arteries, presented at the 7th Annual Symposium on Vascular Innterventions, Birmingham, AL, September 11-13, 1996.
3:50 pm Carotid Stenting: Current Status, Future Prospects Gary S. Roubin, MD, PhD, Jiri Vitek, MD, Sriram Iyer, MD, Jay Yadav, MD, Camillo Gomez, MD Rationale The use of carotid artery stents is a less invasive, potentially safer, and less costly treatment for carotid stenoses. The current standard therapy, carotid endarterectomy, has been shown in randomized trials to be superior to medical management in both symptomatic and asymptomatic patients. However, the translation of these trial results has emphasized the limitations of the surgical approach to the community. The North American Carotid Endarterectomy Surgery Trial (NASCET) was undertaken by a carefully selected group of surgeons and a highly selected subset of patients. The average NASCET site recruited an average of 5 patients per year. Patients with severe cardiopulmonary disorders, the very elderly, and patients with recent strokes were among those not studied in NASCET. To qualify as operators, surgeons had to demonstrate a complication rate of less than 6%. Despite these favorable factors, the perioperative stroke and death rate in NASCET was 6.5%. Recently, a systematic review of a total of 126 studies of endarterectomies concluded that the risk of stroke or death averaged 7.7% in series with neurologic assessment. In the community, Medicare statistics show that the morbidity and mortality is in the range of 10% to 15%. More than 90% of the carotid endarterectomies performed in North America are done under general anesthesia and the average hospital stay is 3 days. Ten percent of patients have cranial nerve palsies; and restenosis after endarterectomy is not uncommon. Finally, an important subset of patients either are at considerably higher risk from endarterectomy or do not have surgery
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