- Email: [email protected]
Intracranial Carotid and Vertebral Artery Interventions: Structural Occlusive Lesion Therapy
Wednesday, March 6, 1996
II 17.
18.
19.
20.
angioplasty: hemodynamic classification of subclavian artery stenoses. Neuroradiology 1985; 27:265-270. Backman DM, Kim RM. Transluminal dilatation for subclavian steal syndrome. AJR 1980; 135:995-996. Motarjeme A, Keifer ]W, Zuska AJ. Percutaneous transluminal angioplasty of the brachiocephalic arteries. AJR 1982; 138: 457-462. Damouth HD Jr, Diamond AB, Rapporport AS, Renner ]W. Angioplasty of subclavian artery stenosis proximal to the vertebral origin. AJNR 1983; 4:1239-1242. Vitek JJ. Subclavian artery angioplasty and the origin of the vertebral artery. Radiology 1989; 170:407-409.
9:20 am Intracranial Carotid and Vertebral Artery Interventions: Structural Occlusive Lesion Therapy Robert D. Ferguson, MD
Intracranial cerebral percutaneous transluminal angioplasty (lCPTA) and stent-assisted cerebral percutaneous transluminal angioplasty (lSACPTA) of carotid and vertebral arteries are new forms of therapy. CPTA refers to highpressure, nonelastomer, balloon dilation of vaso-occlusive target lesions, which may occur as a consequence of atherosclerosis or, less commonly, from spontaneous or traumatic arterial dissection. At present, the clinical effectiveness of ICPTA and ISACPTA is unclear. To my knowledge, no substantive results have yet been published to corroborate the safety and clinical utility of either ICPTA (1) or lSACPTA. The only prospective study experience, to date, comes from the the North American Cerebral Percutaneous Transluminal Angioplasty Register (NACPTAR) (2), a multicenter, protocol-based pilot study of intra- and extracranial CPTA. The impetus for lCPTA and lSACPTA underscores the paucity of acceptable therapeutic alternatives. Nevertheless, despite the dearth of specific accepted alternatives, in most cases, the therapeutic role of cerebral angioplasty needs to be properly defined before widespread implementation is justifiable. Rationale for ICPTA and ISACPTA There are two mechanisms by which intracranial vaso-occlusive abnormalities may reduce blood flow and cause cerebral infarction (3).
270
The first mechanism is in situ atherothromboocclusion, which is encroachment of the plaque (or intima), with or without associated thrombus, on the arterial lumen. The second mechanism is artery-to-artery embolus, which involves liberation of plaque fragments and/or thrombi that narrow or occlude distal elements of the arterial tree. Consequently, there are two main reasons for proposing ICPTA for treatment of structural cerebral vaso-occlusive lesions: (a) to reduce the risk of hemodynamic (low-flow) stroke by increasing the cross-sectional area of the target artery, thereby increasing flow reserve and (b) to favorably alter perilesional rheologic characteristics and restore endothelial function at the target site. We have employed SACPTA, as an adjunct, in cases of suboptimal technical results after angioplasty, when we believed the risk of subsequent occlusion or reocclusion, due to intimal dissection, subplaque hemorrhage, or thromboembolism posed a significant threat to neuronal viability after ICPTA. This strategy is predicated on the assumption that lCPTA, with or without adjunctive stent placement, may prevent cerebral ischemia and infarction in patients at risk for strokes due to thrombotic occlusion, hemodynamic instability, presence of plaque, or dissection-associated thromboembolism. Mechanism of Action The consequences of lCPTA may be similar to those described for lesions with similar morphologic and pathophysiologic characteristics (4,5), that is, endothelial denudation with cracking and splitting of the plaque, along with stretching of the adjacent media and adventitia, leading to aneurysmal dilatation of the target segment and an attendant increase in the crosssectional area (6). Adjuncts to ICPTA and ISACPTA The list of adjunctive pharmaceutical agents and medical devices that affect CPTA study design is large and growing rapidly. We believe that anticoagulation, either alone or in conjunction with platelet antiaggregate medication, for a period of weeks to months, is indicated in most cases of angioplasty and stent placement in the intracranial circulation, irrespective of the underlying pathologic condition. The elicitation of an underlying coagulopathy may justify longer-term use of warfarin sodium. Control of hypertension, elimination of smoking and other
Wednesday, March 6, 1996 nicotine-containing products, as well as lifestyle counseling with regard to diet and exercise are warranted. Stent placement, however, appears to be the most promising adjunctive approach. Evidence available from randomized trials suggests that coronary stent placement produces better initial results and a lower rate of restenosis than angioplasty alone (7,8). In the hands of some operators, stent implantation is successful in up to 95,000 cases (9,10). These results suggest that primary stent placement may be of value in the cerebral circulation. In addition, stent placement may reduce the potential for embolic complications after CPTA, and it is a potential form of vascular rescue for CPTA-induced, traumatic, or spontaneous occlusion due to intimal dissection. Several technical limitations and theoretic concerns suggest caution with respect to the adoption of primary stent placement in the cerebral circulation. These limitations and concerns include deployment collapse after stent placement secondary to intrinsic or extrinsic mechanical interactions; the potential for accelerated restenosis secondary to intimal hyperplasia; the rigidity of currently available stents and their deployment systems; and the presence of inadvertent circulatory exclusion by an intracranial stent of crucial perforating arteries, which effectively limits atraumatic access. Superelastic, crush-resistant materials for stent construction; enhanced design of stents and their delivery systems to ensure atraumatic delivery and continued perfusion of underlying arterial perforators; as well as agents to reduce or eliminate endothelial hyperplasia, delivered locally or perhaps systemically, may in the future permit consideration of primary stent placement. Current Indications ICPTA and SACPTA should be performed only in individuals in whom conventional alternative therapies have failed. These procedures should only be attempted by individuals with formal training in the anatomy, pathophysiology, prognosis, and treatment of intracranial occlusive cerebrovascular disease. Until definitive therapeutic studies are published and accepted by the medical community, all procedures should be performed, except under extraordinary circumstances, under the auspices of an institutional review-board-approved investigational
protocol, with the participation of clinical neuroscientists.
II
In summary, we are still in the early stages of clinical evaluation of ICPTA and ISACPTA. There are no definitive reports concerning the long-term clinical and angiographic results with either procedure. Angioplasty and stent-placement techniques and technology continue to evolve at a rapid pace. Although preliminary results are encouraging, the ultimate role of endovascular intervention for structural intracrania occlusive lesions remains unclear. Although controlled studies are presently impossible given the state of the science, the limited number of skilled operators, and the rapid pace of technologic change, additional basic research as well as prospective randomized studies will very likely be necessary to ultimately establish the safety, efficacy, and clinical utility of ICPTA or ISACPTA in stroke prevention for intracranial carotid and vertebral structural occlusive disease.
References 1. Ferguson R, Ferguson], Lee 1. Extracranial carotid and vertebral stenosis: the future of angioplasty. In: Batjer HH, ed. Cerebrovascular Disease. Raven Press. 2. Ferguson R, Ferguson], Schwarten D, et al. Immediate angiographic results and inhospital central nervous system complications of cerebral percutaneous transluminal angioplasty. Circulation 1993; 88(suppl):1-393. 3. Classification of cerebrovascular diseases. III. Stroke 1990; 21:637--676. 4. Gomez CR. Carotid plaque morphology and the risk for stroke. Stroke 1990; 21: 148-151. 5. Fuster V, Badimon L, Badimon ]], Chesebro ]H. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl] Med 1992; 326:242-250. 6. Landau C, Lange RA, Hillis LD. Percutaneous transluminal angioplasty. N Engl] Med 1994; 330:981-993. 7. Serruys PW, de ]aegere P, Kiemeneij F, et al. A comparison of balloon-expandablestent implantation with balloon angioplasty in patients with coronary artery disease: Benestent Study Group. N Engl] Med 1994; 331:489-495. 8. Fischman DL, Leon MB, Bairn DS, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the
271
Wednesday, March 6, 1996 treatment of coronary artery disease: Stent Restenosis Study Investigators. N Engl J Med 1994; 331:496-501. 9. Haude M, Erbel R, Hafner G, et al. Multicenter results after coronary implantation of balloon-expandable Palmaz-Shatz stents. Z Cardiol 1993; 82:7786. 10. George BS, Voorhes WD III, Roubin GS, et al. Multicenter investigation of coronary stenting to treat acute or threatened closure after percutaneous transluminal angioplasty: clinical and angiographic outcome. J Am Coli Cardiol 1993; 22:135-143.
9:40
am
The Role of Carotid Interventional Trials D. Eugene Strandness, jr, MD
Learning objectives: (1) To understand the relationship between carotid atherosclerosis and its major outcome event-stroke. (2) To understand the structure and results of the large clinical trials. (3) To become knowledgeable about the risks of operation and the risks of arteriography. (4) To be aware of the differences in diameter reduction reported to be significant. (5) To consider the role of arteriography in classifying the degree of stenosis.
272
for entry into the trial, recurrent TIAs after randomization did not constitute an endpoint. Each of these studies showed that the incidence of stroke in the surgical group was lower than in the medical group. Thus, surgery was more effective for preventing stroke. The outcome was as follows: • NASCET. At 2 years, the ipsilateral stroke rate in the medical group was 26% compared with 9% in the surgical group for a >70% diameter-reducing stenosis. • VAST. The stroke rate in the medical group was 9.4% compared with 4.7% in the surgical group (P < 0.056). When events were combined, the difference was highly significant (P < 0.001). These results were obtained with >50% diameter-reducing stenoses. • ACAS. The estimated 5-year risk for stroke in the surgical group was 5.1% and, for the medical group, 11% (P < 0.004) for a >60% diameter-reducing lesion. Interestingly, the combined morbidity and mortality in the surgical groups for each trial would have been predicted based on good historical data. In the NASCET, it was 5.8%; for the VAST, 4.7%; and, for the ACAS, 2.3% (half due to arteriography). The cut-off point for a significant lesion was a diameter reduction of >60%.
The role of carotid atherosclerosis in the production of stroke is recognized, but controversy has existed over the treatment of stroke with carotid endarterectomy. The surgical literature has suggested that the operation could be done with a morbidity and mortality rate of <5% in symptomatic patients and <3% in asymptomatic patients. Nonetheless, skeptics did not accept these results and were not convinced that even at this low risk level the operation could be effective in reducing the incidence of stroke. Apparently, only results from extremely large clinical trials would convince the neurologic community otherwise.
Even given these results, serious problems remain regarding what a significant lesion is. As noted above, each of these trials ended with differing degrees of narrowing as cut-off points. Furthermore, the degree of stenosis needed for operation for asymptomatic patients was less than for symptomatic patients. The issue facing the medical community is: Why is there this difference and how should individual patients be handled based on these data? Finally, arteriography, at least in the ACAS, was as dangerous as an operation.
Consequently, several clinical trials have been conducted or are nearly complete. Major evaluations were the North American Symptomatic Carotid Surgery Trial (NASCET), the Veterans Administration Asymptomatic Trial (VAST), and the Asymptomatic Carotid Surgery Trial (ACAS) 0-4). Outcome endpoints were stroke or death -not transient ischemic attacks (TIAs). While a patient may have experienced a TIA to qualify
1. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. New Engl J Med 1991; 325:445-463. 2. Hobson RW, Weiss DG, Fields WS, et al. Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. N Engl J Med 1993; 328:221-227.
References
II 17.
18.
19.
20.
angioplasty: hemodynamic classification of subclavian artery stenoses. Neuroradiology 1985; 27:265-270. Backman DM, Kim RM. Transluminal dilatation for subclavian steal syndrome. AJR 1980; 135:995-996. Motarjeme A, Keifer ]W, Zuska AJ. Percutaneous transluminal angioplasty of the brachiocephalic arteries. AJR 1982; 138: 457-462. Damouth HD Jr, Diamond AB, Rapporport AS, Renner ]W. Angioplasty of subclavian artery stenosis proximal to the vertebral origin. AJNR 1983; 4:1239-1242. Vitek JJ. Subclavian artery angioplasty and the origin of the vertebral artery. Radiology 1989; 170:407-409.
9:20 am Intracranial Carotid and Vertebral Artery Interventions: Structural Occlusive Lesion Therapy Robert D. Ferguson, MD
Intracranial cerebral percutaneous transluminal angioplasty (lCPTA) and stent-assisted cerebral percutaneous transluminal angioplasty (lSACPTA) of carotid and vertebral arteries are new forms of therapy. CPTA refers to highpressure, nonelastomer, balloon dilation of vaso-occlusive target lesions, which may occur as a consequence of atherosclerosis or, less commonly, from spontaneous or traumatic arterial dissection. At present, the clinical effectiveness of ICPTA and ISACPTA is unclear. To my knowledge, no substantive results have yet been published to corroborate the safety and clinical utility of either ICPTA (1) or lSACPTA. The only prospective study experience, to date, comes from the the North American Cerebral Percutaneous Transluminal Angioplasty Register (NACPTAR) (2), a multicenter, protocol-based pilot study of intra- and extracranial CPTA. The impetus for lCPTA and lSACPTA underscores the paucity of acceptable therapeutic alternatives. Nevertheless, despite the dearth of specific accepted alternatives, in most cases, the therapeutic role of cerebral angioplasty needs to be properly defined before widespread implementation is justifiable. Rationale for ICPTA and ISACPTA There are two mechanisms by which intracranial vaso-occlusive abnormalities may reduce blood flow and cause cerebral infarction (3).
270
The first mechanism is in situ atherothromboocclusion, which is encroachment of the plaque (or intima), with or without associated thrombus, on the arterial lumen. The second mechanism is artery-to-artery embolus, which involves liberation of plaque fragments and/or thrombi that narrow or occlude distal elements of the arterial tree. Consequently, there are two main reasons for proposing ICPTA for treatment of structural cerebral vaso-occlusive lesions: (a) to reduce the risk of hemodynamic (low-flow) stroke by increasing the cross-sectional area of the target artery, thereby increasing flow reserve and (b) to favorably alter perilesional rheologic characteristics and restore endothelial function at the target site. We have employed SACPTA, as an adjunct, in cases of suboptimal technical results after angioplasty, when we believed the risk of subsequent occlusion or reocclusion, due to intimal dissection, subplaque hemorrhage, or thromboembolism posed a significant threat to neuronal viability after ICPTA. This strategy is predicated on the assumption that lCPTA, with or without adjunctive stent placement, may prevent cerebral ischemia and infarction in patients at risk for strokes due to thrombotic occlusion, hemodynamic instability, presence of plaque, or dissection-associated thromboembolism. Mechanism of Action The consequences of lCPTA may be similar to those described for lesions with similar morphologic and pathophysiologic characteristics (4,5), that is, endothelial denudation with cracking and splitting of the plaque, along with stretching of the adjacent media and adventitia, leading to aneurysmal dilatation of the target segment and an attendant increase in the crosssectional area (6). Adjuncts to ICPTA and ISACPTA The list of adjunctive pharmaceutical agents and medical devices that affect CPTA study design is large and growing rapidly. We believe that anticoagulation, either alone or in conjunction with platelet antiaggregate medication, for a period of weeks to months, is indicated in most cases of angioplasty and stent placement in the intracranial circulation, irrespective of the underlying pathologic condition. The elicitation of an underlying coagulopathy may justify longer-term use of warfarin sodium. Control of hypertension, elimination of smoking and other
Wednesday, March 6, 1996 nicotine-containing products, as well as lifestyle counseling with regard to diet and exercise are warranted. Stent placement, however, appears to be the most promising adjunctive approach. Evidence available from randomized trials suggests that coronary stent placement produces better initial results and a lower rate of restenosis than angioplasty alone (7,8). In the hands of some operators, stent implantation is successful in up to 95,000 cases (9,10). These results suggest that primary stent placement may be of value in the cerebral circulation. In addition, stent placement may reduce the potential for embolic complications after CPTA, and it is a potential form of vascular rescue for CPTA-induced, traumatic, or spontaneous occlusion due to intimal dissection. Several technical limitations and theoretic concerns suggest caution with respect to the adoption of primary stent placement in the cerebral circulation. These limitations and concerns include deployment collapse after stent placement secondary to intrinsic or extrinsic mechanical interactions; the potential for accelerated restenosis secondary to intimal hyperplasia; the rigidity of currently available stents and their deployment systems; and the presence of inadvertent circulatory exclusion by an intracranial stent of crucial perforating arteries, which effectively limits atraumatic access. Superelastic, crush-resistant materials for stent construction; enhanced design of stents and their delivery systems to ensure atraumatic delivery and continued perfusion of underlying arterial perforators; as well as agents to reduce or eliminate endothelial hyperplasia, delivered locally or perhaps systemically, may in the future permit consideration of primary stent placement. Current Indications ICPTA and SACPTA should be performed only in individuals in whom conventional alternative therapies have failed. These procedures should only be attempted by individuals with formal training in the anatomy, pathophysiology, prognosis, and treatment of intracranial occlusive cerebrovascular disease. Until definitive therapeutic studies are published and accepted by the medical community, all procedures should be performed, except under extraordinary circumstances, under the auspices of an institutional review-board-approved investigational
protocol, with the participation of clinical neuroscientists.
II
In summary, we are still in the early stages of clinical evaluation of ICPTA and ISACPTA. There are no definitive reports concerning the long-term clinical and angiographic results with either procedure. Angioplasty and stent-placement techniques and technology continue to evolve at a rapid pace. Although preliminary results are encouraging, the ultimate role of endovascular intervention for structural intracrania occlusive lesions remains unclear. Although controlled studies are presently impossible given the state of the science, the limited number of skilled operators, and the rapid pace of technologic change, additional basic research as well as prospective randomized studies will very likely be necessary to ultimately establish the safety, efficacy, and clinical utility of ICPTA or ISACPTA in stroke prevention for intracranial carotid and vertebral structural occlusive disease.
References 1. Ferguson R, Ferguson], Lee 1. Extracranial carotid and vertebral stenosis: the future of angioplasty. In: Batjer HH, ed. Cerebrovascular Disease. Raven Press. 2. Ferguson R, Ferguson], Schwarten D, et al. Immediate angiographic results and inhospital central nervous system complications of cerebral percutaneous transluminal angioplasty. Circulation 1993; 88(suppl):1-393. 3. Classification of cerebrovascular diseases. III. Stroke 1990; 21:637--676. 4. Gomez CR. Carotid plaque morphology and the risk for stroke. Stroke 1990; 21: 148-151. 5. Fuster V, Badimon L, Badimon ]], Chesebro ]H. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl] Med 1992; 326:242-250. 6. Landau C, Lange RA, Hillis LD. Percutaneous transluminal angioplasty. N Engl] Med 1994; 330:981-993. 7. Serruys PW, de ]aegere P, Kiemeneij F, et al. A comparison of balloon-expandablestent implantation with balloon angioplasty in patients with coronary artery disease: Benestent Study Group. N Engl] Med 1994; 331:489-495. 8. Fischman DL, Leon MB, Bairn DS, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the
271
Wednesday, March 6, 1996 treatment of coronary artery disease: Stent Restenosis Study Investigators. N Engl J Med 1994; 331:496-501. 9. Haude M, Erbel R, Hafner G, et al. Multicenter results after coronary implantation of balloon-expandable Palmaz-Shatz stents. Z Cardiol 1993; 82:7786. 10. George BS, Voorhes WD III, Roubin GS, et al. Multicenter investigation of coronary stenting to treat acute or threatened closure after percutaneous transluminal angioplasty: clinical and angiographic outcome. J Am Coli Cardiol 1993; 22:135-143.
9:40
am
The Role of Carotid Interventional Trials D. Eugene Strandness, jr, MD
Learning objectives: (1) To understand the relationship between carotid atherosclerosis and its major outcome event-stroke. (2) To understand the structure and results of the large clinical trials. (3) To become knowledgeable about the risks of operation and the risks of arteriography. (4) To be aware of the differences in diameter reduction reported to be significant. (5) To consider the role of arteriography in classifying the degree of stenosis.
272
for entry into the trial, recurrent TIAs after randomization did not constitute an endpoint. Each of these studies showed that the incidence of stroke in the surgical group was lower than in the medical group. Thus, surgery was more effective for preventing stroke. The outcome was as follows: • NASCET. At 2 years, the ipsilateral stroke rate in the medical group was 26% compared with 9% in the surgical group for a >70% diameter-reducing stenosis. • VAST. The stroke rate in the medical group was 9.4% compared with 4.7% in the surgical group (P < 0.056). When events were combined, the difference was highly significant (P < 0.001). These results were obtained with >50% diameter-reducing stenoses. • ACAS. The estimated 5-year risk for stroke in the surgical group was 5.1% and, for the medical group, 11% (P < 0.004) for a >60% diameter-reducing lesion. Interestingly, the combined morbidity and mortality in the surgical groups for each trial would have been predicted based on good historical data. In the NASCET, it was 5.8%; for the VAST, 4.7%; and, for the ACAS, 2.3% (half due to arteriography). The cut-off point for a significant lesion was a diameter reduction of >60%.
The role of carotid atherosclerosis in the production of stroke is recognized, but controversy has existed over the treatment of stroke with carotid endarterectomy. The surgical literature has suggested that the operation could be done with a morbidity and mortality rate of <5% in symptomatic patients and <3% in asymptomatic patients. Nonetheless, skeptics did not accept these results and were not convinced that even at this low risk level the operation could be effective in reducing the incidence of stroke. Apparently, only results from extremely large clinical trials would convince the neurologic community otherwise.
Even given these results, serious problems remain regarding what a significant lesion is. As noted above, each of these trials ended with differing degrees of narrowing as cut-off points. Furthermore, the degree of stenosis needed for operation for asymptomatic patients was less than for symptomatic patients. The issue facing the medical community is: Why is there this difference and how should individual patients be handled based on these data? Finally, arteriography, at least in the ACAS, was as dangerous as an operation.
Consequently, several clinical trials have been conducted or are nearly complete. Major evaluations were the North American Symptomatic Carotid Surgery Trial (NASCET), the Veterans Administration Asymptomatic Trial (VAST), and the Asymptomatic Carotid Surgery Trial (ACAS) 0-4). Outcome endpoints were stroke or death -not transient ischemic attacks (TIAs). While a patient may have experienced a TIA to qualify
1. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. New Engl J Med 1991; 325:445-463. 2. Hobson RW, Weiss DG, Fields WS, et al. Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. N Engl J Med 1993; 328:221-227.
References