- Email: [email protected]
In-stent restenosis after carotid angioplasty-stenting: Incidence and management
In-stent restenosis after carotid angioplastystenting: Incidence and management Elie Y. Chakhtoura, MD, Robert W. Hobson II, MD, Jonathan Goldstein, MD, Gregory T. Simonian, MD, Brajesh K. Lal, MD, Paul B. Haser, MD, Michael B. Silva, Jr, MD, Frank T. Padberg, Jr, MD, Peter J. Pappas, MD, and Zafar Jamil, MD, Newark, NJ Purpose: Carotid angioplasty-stenting (CAS) has been advocated as an alternative to carotid endarterectomy (CEA) in patients with restenotic lesions after prior CEA, primary stenoses with significant medical comorbidities, and radiationinduced stenoses. The incidence of restenosis after CAS and its management remains ill defined. We evaluated the incidence and management of in-stent restenosis after CAS. Methods: Patients with asymptomatic (61%) and symptomatic (39%) carotid stenosis of ≥ 80% underwent CAS between September 1996 and May 2000; there were 50 procedures and 46 patients (26 men and 20 women). All patients were followed up clinically and underwent duplex ultrasonography (DU) at 3- to 6-month intervals. In-stent restenoses ≥ 80% detected with DU were further evaluated by means of angiography for confirmation of the severity of stenosis. Results: No periprocedural or late strokes occurred in the 50 CAS procedures during the 30-day follow-up period. One death (2.2%) that resulted from myocardial infarction was observed 10 days after discharge following CAS. During a mean follow-up period of 18 ± 10 months (range, 1-44 months), in-stent restenosis was observed after four (8%) of the 50 CAS procedures. Angiography confirmed these high-grade (≥ 80%) in-stent restenoses, which were successfully treated with balloon angioplasty (3) or angioplasty and restenting (1). No periprocedural complications occurred, and these patients remained asymptomatic and without recurrent restenosis over a mean follow-up time of 10 ± 6 months. Conclusions: We recommend CAS for post-CEA restenosis, primary stenoses in patients with high-risk medical comorbidities, and radiation-induced stenoses. In-stent restenoses occurred after 8% of CAS procedures and were managed without complications with repeat angioplasty or repeat angioplasty and restenting. (J Vasc Surg 2001;33:220-6.)
Carotid angioplasty-stenting (CAS) has been recommended by some clinicians as an alternative to carotid endarterectomy (CEA).1-4 However, as emphasized in the recent consensus statement from the American Heart Association,5 this new catheter-based procedure should be restricted to limited subgroups of patients, whereas the gold standard of endarterectomy remains the preferred method for the management of most patients with carotid occlusive disease. CEA has emerged as the optimal treatment for symptomatic and asymptomatic patients with high-grade extracranial carotid stenoses.6-10 However, according to the conclusions of a multidisciplinary panel at the recent Montefiore Vascular Symposium,11 subgroups of patients including high-risk patients with significant medical comorbidities, those with carotid restenosis after prior CEA, those with anatomically inaccessible lesions above the second rib, and those with radiation-induced stenoses should currently be considered for CAS. As an example, our group12 recently From the Division of Vascular Surgery, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, and the Division of Cardiology, St Michael’s Medical Center. Competition of interest: nil. Presented at the meeting of the American Association for Vascular Surgery Toronto, Ontario, Canada, Jun 2000. Reprint requests: Robert W. Hobson II MD, Division of Vascular Surgery, Department of Surgery, UMDNJ-NJMS, Medical Science Building, G532, 185 South Orange Avenue, Newark, NJ 07103 (e-mail: [email protected]). Copyright © 2001 by The Society for Vascular Surgery and The American Association for Vascular Surgery. 0741-5214/2001/$35.00 + 0 24/6/111880 doi:10.1067/mva.2001.111880
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documented the comparability of results between CAS and surgical management for restensosis after primary CEA. However, in the absence of randomized clinical trial procedures,5 we are currently unwilling to expand the use of CAS beyond these defined subgroups of patients.11 An additional concern about the CAS procedure has been the potential for development of in-stent restenosis.12,13 This complication has been observed after coronary stenting in 16% to 59% of cases,14-16 whereas in-stent restenosis after iliac stenting has been observed in 13% to 39% of reported series.17-19 In-stent restenosis after CAS has been reported in only 4% to 5% of cases (Table I)3,4,20,21; however, clinical follow-up has been relatively short, generally less than 12 months. The purpose of the current study is to determine the incidence of in-stent restenosis after CAS in our clinical series and to evaluate the utility of endovascular techniques for the management of in-stent restenosis. METHODS Patient population. Between September 1996 and May 2000, 50 CAS procedures were performed on 46 consecutive patients according to a protocol approved by the Institutional Review Board to investigate the feasibility of CAS. Twenty-six patients were men (57%), and 20 were women (43%) with a mean age of 69 ± 11 years. Symptomatic and asymptomatic high-grade stenoses (≥ 80%) were included in this protocol. Baseline clinical characteristics of the group are summarized in Table II. Of the 50 stenotic lesions, 40 (80%) were post-CEA restenoses, 9 (18%) were primary lesions in patients with critical two- or three-vessel coronary artery disease, and 1
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Table I. Incidence of in-stent restenosis after CAS
Diethrich et al3 Theron20 Yadav et al4 Wholey et al21
n
Restenosis (%)
Follow-up (mo)
110 93 126 2048
4.5 4. 4.9 4.8
8 12 6 6
(2%) was a stenosis that was complicating childhood cervical radiation therapy. Clinical protocol and follow-up. Clinical, angiographic, and procedural data were prospectively collected. Prior to and 24 hours after CAS, patients were examined by the vascular surgeon, interventionist, or, in some instances, an independent neurologist. All patients were followed up prospectively at 3- to 6-month intervals clinically and underwent duplex ultrasonography (DU). Restenotic lesions detected with DU were further evaluated with angiography for confirmation of the severity of stenosis. CAS protocol. CAS was performed as previously described12 (Fig 1). Patients were pretreated with aspirin (325 mg/d) for at least 2 days before the procedure and with either ticlopidine (250 mg twice daily) or clopidogrel (75 mg once daily) after a loading dose that was given the day of the procedure. Aspirin and one of the other two antiplatelet agents were continued for 4 weeks after CAS with aspirin therapy alone thereafter. Patients received intravenous sedation, and local anesthesia was achieved with infiltration of 1% lidocaine (Xylocaine). Venous access was secured in all patients, and a transvenous pacemaker was routinely available. Standard retrograde access was performed in the common femoral artery, and a 6F vascular sheath was inserted. Weight-adjusted heparin was administered (70 U/kg), and the activated clotting time was maintained at 225 to 250 seconds throughout the procedure. A 0.035-in guidewire (Wholey modified J, 175-cm; Mallinkrodt, St Louis, MO,) in a 5F Vitek or HN2 cerebral diagnostic catheter (Cook, Bloomington, Ind) was introduced for selective cannulation of the common carotid artery (CCA). Digital angiography was performed to confirm the severity of stenosis. Subsequently, the diagnostic catheter was exchanged over a 0.035-in exchangelength (260 cm) Amplatz Super Stiff guidewire (Meditech/Boston Scientific, Natick, Mass) for an 8F 100cm long sheath that was passed into the CCA. The stenosis was crossed with a 0.018-in Roadrunner extrasupport guidewire (Cook), and prestent dilatation was performed with low-profile 4 × 30-mm balloon catheters inflated to 8 atm, followed by stent deployment. Poststent dilatation was performed with 5- or 6-mm high-pressure balloons inflated to 12 atm. In the 46 patients, 50 stents were used during the carotid interventions. One patient underwent staged bilateral CAS procedures with Wallstents for postCEA restenoses, and three patients had use of a second stent (2 Wallstents and 1 Palmaz stent) for separate stenoses in the CCA. Of the 50 stents, 49 (98%) were self-
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Table II. Baseline clinical characteristics of the study group (N = 46)
Men Women Asymptomatic (> 80%) Symptomatic Hemispheric TIA Amaurosis fugax Global symptoms Diabetes Hypertension Smoker Hypercholesterolemia Coronary artery disease
n
%
26 20 28 18 6 2 10 15 39 23 23 25
57 43 61 39 13 4 22 33 85 50 50 54
expanding Wallstents, 8 × 20 mm and 10 × 20 mm (Meditech/Boston Scientific, Minneapolis, Minn), and 1 (2%) was a Palmaz P-154 stent (Johnson and Johnson Interventional Systems Co, Warren, NJ). On completion of the procedure, ipsilateral carotid and intracranial angiography was performed to assess technical success and to exclude distal cerebral embolization. Vascular sheaths were removed after the procedure, and femoral hemostasis was accomplished by means of a transcatheter closure device, Prostar XL (Perclose/Abbott, Redwood City, Calif). Imaging criteria and end points. Restenosis detected with DU was classified as moderate (50%-79%) and severe (≥ 80%). Quantitative angiographic analysis was performed on all arteries before and after CAS and for verification of restenosis detected with follow-up DU. An on-line software program of quantitative angiographic analysis was used (MDQM; MEDCON Telemedicine Technology, Inc, Livingston, NJ). With criteria from the North American Symptomatic Carotid Endarterectomy Trial,6 the degree of stenosis was determined by comparison of the least transverse diameter at the maximal stenosis with the reference diameter of the distal internal carotid artery once its walls became parallel. The minimal lumen diameter was measured after calibration of the system with the known diameter of the guiding catheter. Patients with high-grade restenosis (> 80%) revealed by DU underwent confirmatory angiography before reinterventions. RESULTS Demographics and outcome. CAS was performed on 50 carotid stenoses in 46 patients (Table II). There were 26 men (57%) and 20 women (43%). Of the 46 patients, 28 were asymptomatic (61%) and 18 were symptomatic (39%). Of the symptomatic group, six patients had hemispheric transient ischemic attacks (TIAs) without neurologic deficits, and two patients had amaurosis fugax. The remaining 10 patients complained of global symptoms, including severe lightheadedness, syncopal episodes, or both, but without any lateralizing neurologic deficits. After CAS, all patients were followed up clinically and
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A
B
C
D
Fig 1. A, Selective angiography in symptomatic patient presenting with single episode of amaurosis fugax 11 months after prior right CEA, demonstrating focal high-grade restenosis (arrow). B, Poststent deployment angioplasty resulted in technically satisfactory angiographic results (arrows refer to length of stent). C, In-stent restenosis was defined angiographically in two areas (arrows) in this patient 6 months after CAS. D, Angioplasties of both areas reduced lesions to < 30% residual stenoses (arrows), which have not recurred during a 14-month follow-up.
underwent DU at 3- to 6-month intervals during a mean follow-up time of 18 ± 10 months (range, 1-44 months). No minor or major strokes were observed in this series of 50 CAS procedures. Two TIAs were
observed during CAS. Each resolved spontaneously within minutes of its onset and without residual deficits. One patient (2.2%) died in this series. This 72-year-old woman had undergone a two-vessel coronary angio-
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plasty with stenting 2 days before CAS. Ten days after her discharge from the hospital, she died suddenly, presumably as a result of myocardial infarction. All other patients have remained asymptomatic. In-stent restenosis. Six in-stent restenoses were observed on follow-up DU: two (4%) were classified as moderate (50%-79%), and four (8%) were severe (> 80%). After evaluation with angiography, the two moderate stenoses were found to have < 50% stenosis and were not treated. The high-grade stenoses (> 80%) were confirmed in the other four patients, thus meeting the criterion for reintervention. Three of the treated in-stent restenoses developed in patients after CAS for post-CEA restenosis, whereas the fourth restenosis developed after an initial CAS procedure for radiation-induced stenosis. The clinical characteristics of patients with in-stent restenosis are outlined in Table III. Although these patients were asymptomatic, reintervention was recommended because of the severity of their restenosis (≥ 80%) and the presence of accompanying contralateral occlusion. In-stent restenosis was observed at a mean interval of 13 ± 7 months (range, 6-21 months) after the original CAS procedure. Three of the four restenoses were treated with angioplasty alone (Fig 2). The remaining patient was treated with angioplasty and restenting with a Palmaz stent. All four patients remained asymptomatic and without recurrent restenosis over a mean follow-up time of 10 ± 6 months (range, 1-14 months). DISCUSSION Prospective randomized clinical trials have confirmed the efficacy of CEA over optimal medical management alone for the treatment of symptomatic6-8 and asymptomatic9-10 patients with high-grade extracranial carotid stenoses. However, CAS has emerged as an alternative treatment modality, especially in high-risk patients. An endovascular approach may be better suited for the treatment of patients with restenotic lesions after CEA, with primary stenoses with high-risk medical comorbidities, or with radiation-induced stenoses. Although our group reported comparable results between CAS and surgical management of post-CEA restenoses, 12 surgical intervention has generally been associated with a higher rate of complications than those reported after primary CEA. Bartlett et al22 reported a 30-day stroke and death rate of 6.0%, whereas Das et al23 reported 4.6% and Treiman et al24 reported 3.5%. All noted increased risks of transient cranial nerve palsies. These results have stimulated interest in the use of CAS for post-CEA restenoses.1,12,25,26 Coronary stenting has been associated with significantly lower rates of angiographic and clinical restenosis than angioplasty alone.27,28 This salutary effect may be due to the stent’s ability to provide predictably larger arterial lumens.29 However, myointimal hyperplasia accompanies virtually every stent placement in the coronary, iliac, or carotid system, and some patients have hyperplasia of sufficient magnitude to cause flow-limiting restenosis.
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Table III. Clinical characteristics of the patients with instent restenosis (n = 4)
Men Women Asymptomatic (> 80%) Diabetes Hypertension Smoker Hypercholesterolemia Coronary artery disease
n
%
1 3 4 1 2 2 1 0
25 75 100 25 50 50 25 0
Restenosis has been reported to be as high as 59% after coronary angioplasty-stenting16 and 39% after iliac interventions.19 However, on the basis of collected clinical data from 24 centers, Wholey et al21 reported a rate of restenosis after CAS of only 4.8% (n = 2048) at a mean of 6 months of clinical follow-up. Diethrich et al3 defined a restenosis rate of 4.5% after 8 months of follow-up, whereas Yadav et al4 reported 4.9% at 6 months and Theron20 reported 4% at 12 months. The basis for this apparent lower incidence of in-stent restenosis in the carotid circulation as compared with the coronary and iliac vasculatures remains unknown. We investigated the incidence of in-stent restenosis after CAS in a high-risk surgical group for a follow-up interval of 18 ± 10 months (range, 1-44 months). We observed four patients (8.7%) with significant (≥ 80%) in-stent restenosis. Three of the patients were treated with angioplasty alone (Fig 2), and the fourth patient was treated with angioplasty and restenting. Although our series of 50 CAS procedures has been restricted to defined subgroups of patients,11 our cases of in-stent restenosis have been observed in patients after prior CEA or radiation therapy. Thus, our reported incidence of in-stent restenosis may be more reflective of CAS performed for post-CEA restenosis. Although myointimal hyperplasia with smooth muscle cell proliferation is the predominant mechanism leading to in-stent restenosis30 as well as the underlying mechanism for restenosis occurring within 2 to 3 years of CEA,22-24 stent implantation in a preexistent hyperplastic process may be associated with a higher incidence of in-stent restenosis than after CAS for primary stenosis. Currently, we recommend CAS for post-CEA restenosis, primary stenoses in high-risk patients, and radiationinduced stenosis. The 30-day stroke and death rate in our series was 2.2%. Although in-stent restenosis was detected in four (8%) of the 50 CAS procedures, treatment with angioplasty or angioplasty and re-stenting was effective and not associated with neurologic complications. None of these lesions has recurred during clinical or DU followup. All patients continue to be asymptomatic, and no further operative interventions have been performed in these post-CAS patients.
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B
A
Fig 2. A, Angiographic demonstration of focal in-stent restenosis developing at upper aspect of WallStent (arrow) 7 months after CAS. B, Treatment with angioplasty and placement of Palmaz stent produced a technically satisfactory angiographic result (notice that external carotid artery was occluded during a prior operative intervention; stenosis at proximal end of prior CEA site demonstrated no pressure gradient and was not treated).
REFERENCES 1. Theron J, Raymond J, Casasco A, Courtheoux F. Percutaneous angioplasty of atherosclerotic and postsurgical stenosis of carotid arteries. AJNR Am J Neuroradiol 1987;8:495-500. 2. Roubin GS, Yadav S, Iyer SS, Vitek J. Carotid stent-supported angioplasty: a neurovascular intervention to prevent stroke. Am J Cardiol 1996;78 Suppl 3A:8-12. 3. Diethrich EB, Ndiye M, Reid BD. Stenting in the carotid artery: initial experience in 110 patients. J Endovasc Surg 1996;3:42-62. 4. Yadav JS, Roubin GS, Iyer S, Vitek J, King P, Jordan WD, et al. Elective stenting of the extracranial carotid arteries. Circulation 1997;95:3 76-81. 5. Bettmann MA, Katzen BT, Whisnant J, Cochairs: Brant-Zawadzki M, Broderick JP, et al. Carotid stenting and angioplasty: a statement for healthcare professionals from the Councils on Cardiovascular Radiology, Stroke, Cardiothoracic and Vascular Surgery, Epidemiology and Prevention, and Clinical Cardiology, American Heart Association. Stroke 1998;29:336-48. 6. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;325:445-53. 7. European Carotid Surgery Trialists’ Collaborative Group. MCR European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. Lancet 1991;337:1235-43. 8. Mayberg MR, Wilson SE, Yatsu F, VA Symptomatic Carotid Stenosis Group. Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. JAMA 1991;266:3289-94. 9. Hobson RW, Weiss DG, Fields WS, Goldstone J, Moore WS, Towne
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JB, et al. Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. N Engl J Med 1993;328:221-7. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid stenosis. JAMA 1995;273:1421-8. Veith FT, Amor M, Hobson RW, et al. Consensus panel on carotid angioplasty-stent. J Vasc Surg. In press 2000. Hobson RW, Goldstein JE, Jamil Z et al. Carotid restenosis: operative and endovascular management. J Vasc Surg 1999;29:228-38. O’Hara PJ. Carotid restenosis: operative and endovascular management [discussion]. J Vasc Surg 1999;29:236-7. Laham RJ, Carrozza JP, Berger C, et al. Long-term (4- to 6-year) outcome of Palmaz-Schatz stenting: paucity of late clinical stent-related problems. J Am Coll Cardiol 1996;28:820-6. Edelman ER, Rogers C. Hoop dreams: stent without restenosis. Circulation 1996;94:1199-202. Kastrati A, Schomig A, Elezi S, et al. Predictive factors of restenosis after coronary stent placement. J Am Coll Cardiol 1997;30: 1428-36. Cikrit DF, Gustafson PA, Dalsing MC, Harris VJ, Lalka SG, Sawchuk AP, et al. Long-term follow-up of the Palmaz stent for iliac occlusive disease. J Vasc Surg 1995;118:608-13. Becquemin JP, Allaire E, Qvarfordt P, Desgranges P, Kobeiter H, Melliere D. Surgical transluminal iliac angioplasty with selective stenting: long-term results assessed by means of duplex scanning. J Vasc Surg 1999;23:422-9. Sapoval MR, Chatellier G, Long AL, Rovani C, Pagny JY, Raynaud AC, et al. Self-expandable stents for the treatment of iliac artery obstructive lesions: long-term success and prognostic factors. AJR Am J Roentgenol 1996;165:1173-9.
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20. Theron JG. Carotid artery stenosis: treatment with protected balloon angioplasty and stent placement. Radiology 1996;201:627-36. 21. Wholey MH, Wholey M, Bergeron P, Diethrich EB, Henry M, Laborde JC, et al. Current global status of carotid artery stent placement. Cathet Cardiovasc Diagn 1998;44:1-6. 22. Barlett FF, Rapp JH, Goldstone J, Ehrenfeld WK, Stoney RJ. Recurrent carotid stenosis: operative strategy and late results. J Vasc Surg 1987;5:452-6. 23. Das MD, Hertzer NR, Ratliff NB, O’Hara PJ, Beven EG. Recurrent carotid stenosis: a five-year series of 65 operations. Ann Surg 1985;202:28-35. 24. Treiman GS, Jenkins JM, Edwards WH, Barlow W, Edwards WH, Martin RS, et al. The evolving surgical management of recurrent carotid stenosis. J Vasc Surg 1992;16:354-63. 25. Bergeron P, Chambran P, Benichou H, Alessandri C. Recurrent carotid disease: will stents be an alternative to surgery? J Endovasc Surg 1996;3:76-9. 26. Yadav JS, Roubin GS, King P, Iyer S, Vitek J. Angioplasty and stent-
Submitted Jun 12, 2000; accepted Sep 15, 2000.
DISCUSSION Dr Timothy M. Sullivan (Greenville, SC). Since my time is short and given Dr Porter’s previous comments, I’ll try and cut to the chase. First, Dr Hobson, given the relatively benign nature of recurrent stenosis following carotid endarterectomy, there are those who recommend treatment of these lesions only when they become symptomatic. Given a combined risk of stroke and death of 2.2% in your series, is it really reasonable to subject these patients, the majority of whom did not have hemispheric symptoms, to an experimental and unproven therapy? Second, as a vascular surgeon who performs carotid intervention, I’d like to know when to consider operation for my patients with multiple recurrences and when to consider reintervention? Third, the Wallstent has been shown to be a fairly efficient machine for inducing myointimal hyperplasia in other arterial beds, most notably the superficial femoral artery. Do you think your results would be better if you had used a different stent, and which stent are you currently using? Next, when considering interventional therapy for recurrent stenoses following endarterectomy, do you differentiate between early restenosis, which is likely myointimal and probably low risk for intervention, and late restenosis, which is atherosclerotic and may be higher risk for intervention? Finally, given the fairly low rate of restenosis that your group and others have documented, and with the advent of cerebral protection devices, the question that begs to be asked is, what are your predictions for the fate of carotid endarterectomy over the coming decade? Although Dr Hobson has reported reasonable results for the interventional treatment of carotid restenoses, it is important that these results not be extrapolated to angioplasty for de novo carotid stenoses. These are, however, important data. It is even more important that vascular surgeons be involved in the review of this new technology so that hard, peer-reviewed, and honest data are utilized to dictate medical care for our patients, rather than reports of anecdotal experiences from investigators who may have a personal and financial interest in the success of this new procedure. Thank you. Dr Robert W. Hobson II. Thanks very much, Dr Sullivan. Those are excellent questions. First of all, we know that the restenotic lesion has a low neurological event rate. However, data on restenoses ≥ 80% and their possible progression to occlusion are not well defined. As a result, we selected the 80% diameter-reducing stenosis as the threshold for intervention. I recognize that this is controversial, and some of you may not choose intervention in these cases. However, this became part of our clinical protocol. With regard to reoperations for restenosis, we have not found that necessary during the last 4 years. Angioplasty and stenting
appear to be a reasonable alternative for initial cases of restenosis. The Wallstent is not the stent of choice in my opinion. If you remember the first case I presented with a focal restenosis, we used a 40-mm stent, which resulted in a lengthy segment of normal internal carotid being covered with the stainless steel stent. Ultimately, if recurrent restenosis develops, operation with a venous interposition graft may be required. However, we have not yet encountered such a case. The newer nitinol technology will offer us advantages in more precise placement of the stent and probably with equivalent or perhaps even lower in-stent restenosis rates. Early restenotic lesions due to myointimal hyperplasia (within 3 years of CEA) were selected preferentially in this series because of an anticipated lower incidence of embolization during CAS. For stenoses occurring beyond the 3-year interval, selection would be based in part on the results of duplex ultrasonography. For lesions comparable to primary atherosclerotic plaques, reoperation should be considered rather than CAS, until cerebral protection devices are available. As far as our reported incidence of in-stent restenosis and the ultimate decision about using this procedure in primary stenosis patients, clearly, a need exists for randomized clinical trial methodology. Our reported case series, performed over the last 4 years, accounted for less than 8% of our procedures in patients with cerebrovascular insufficiency. Restenosis is an example of one of the subsets of patients that the American Heart Association’s Consensus Panel has suggested as reasonable for angioplasty and stenting. But none of us will be prepared to move away from the gold standard of carotid endarterectomy based on retrospective evidence. Until we have data from randomized, prospective clinical trials, endarterectomy will remain the mainstay of treatment of patients with symptomatic and asymptomatic extracranial carotid occlusive disease. Thank you. Dr. Kevin G. Burnand (London, United Kingdom). Dr Hobson, thank you very much for that series. Are you actually suggesting to us that the carotid is some sort of privileged site in terms of the restenosis rate? Are you surprised at the difference in restenosis rates from stents compared from the angioplasty series that have been recorded? Dr Hobson. I was surprised. Given the incidence of restenosis after angioplasty-stenting in the coronary circulation and the iliac arteries, many of my partners predicted that we’d be intervening on in-stent restenosis cases by percutaneous techniques or perhaps skull-based operations. However, our results have suggested a much lower incidence of recurrent restenosis following CAS. As emphasized by Dr Sullivan, the earlier lesions are myointimal hyperplasia. It is possible that the carotid artery’s high-flow rate and low cerebrovascular resistance may result in an incidence of myointimal hyperplasia that is lower than associated with other vasculatures.
27.
28.
29.
30.
ing for restenosis after carotid endarterectomy: initial experience. Stroke 1996;27:2075-9. Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N Engl J Med 1994;331:496-501. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heydrickx G, et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med 1994;331:489-95. Kuntz RE, Gibson CM, Nobuyoshi M, Baim DS. Generalized model of restenosis after conventional balloon angioplasty, stenting and directional atherectomy. J Am Coll Cardiol 1993;21:15-25. Mintz GS, Popma JJ, Hong MK, et al. Intravascular ultrasound to discern device-specific effects and mechanisms of restenosis. Am J Cardiol 1996;78 Suppl 3A:18-22.
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Dr William D. Turnipseed (Madison, Wis). We’re all aware of the fact that whether you treat carotid stenosis by primary stenting or carotid surgery, hyperplastic recurrence is a fact of life. My concern is when there are tertiary and/or quartenary recurrences that are often encountered, after re-endarterectomy and/or patch placement with the same misery of recurrent stenosis thereafter. It would seem at first blush that stenting would be an attractive way to deal with this kind of recurrent lesion. From bad personal experience, I would raise the question of whether there are relative contraindications for using stents in patients who have previous prosthetic patch placement for recurrent stenosis. We have had two experiences, one in the iliac and one in the carotid artery, where the patches disrupted late after the initial successful angioplasty. These became infected. Let me tell you, salvage procedures for an infected mycotic aneurysm with a stent in place are very challenging operations. Dr Hobson. Bill, thank you for your comments. I’ll take your word that it is a challenging operation. However, with careful sizing of the stent, this is the preferred procedure for postendarterectomy restenosis. It is associated with a low complication rate. If in-stent restenosis does occur, at least in our series, subsequent endovascular management is an option that appears to be reasonable and safe. It
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would also appear that the presence of a synthetic patch is not a contraindication to the procedure. Dr George Andros (Encino, Calif). I’m not going to comment on the appropriateness of these procedures or the procedure itself. And we scarcely need anybody else in the room to comment on the controversies, as John is up there. But we certainly have to take this as a landmark paper. To my recollection this is the first paper that I know of in this Society—and it’s particularly appropriate that it’s given by the president-elect—in which all the endoluminal procedures were done by a vascular surgeon. And I think that signifies an end to when we’re going to see vascular surgeons stand up here and present the work done by their interventional radiologists where they might not even have been in town when the cases were done and they weren’t really sure what kind of balloon was used in-stent. So I congratulate you, Bob. I think that you’ve shown us the future, and it’s that vascular surgeons have to present their own endovascular work. Dr Hobson. Thank you, George. We did collaborate with colleagues in cardiology. However, I scrubbed on every case, and our fellow in vascular surgery has been an important part of this program. I agree that it is time for vascular surgery to present its own results on endovascular procedures. Thank you very much.
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Carotid angioplasty-stenting (CAS) has been recommended by some clinicians as an alternative to carotid endarterectomy (CEA).1-4 However, as emphasized in the recent consensus statement from the American Heart Association,5 this new catheter-based procedure should be restricted to limited subgroups of patients, whereas the gold standard of endarterectomy remains the preferred method for the management of most patients with carotid occlusive disease. CEA has emerged as the optimal treatment for symptomatic and asymptomatic patients with high-grade extracranial carotid stenoses.6-10 However, according to the conclusions of a multidisciplinary panel at the recent Montefiore Vascular Symposium,11 subgroups of patients including high-risk patients with significant medical comorbidities, those with carotid restenosis after prior CEA, those with anatomically inaccessible lesions above the second rib, and those with radiation-induced stenoses should currently be considered for CAS. As an example, our group12 recently From the Division of Vascular Surgery, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, and the Division of Cardiology, St Michael’s Medical Center. Competition of interest: nil. Presented at the meeting of the American Association for Vascular Surgery Toronto, Ontario, Canada, Jun 2000. Reprint requests: Robert W. Hobson II MD, Division of Vascular Surgery, Department of Surgery, UMDNJ-NJMS, Medical Science Building, G532, 185 South Orange Avenue, Newark, NJ 07103 (e-mail: [email protected]). Copyright © 2001 by The Society for Vascular Surgery and The American Association for Vascular Surgery. 0741-5214/2001/$35.00 + 0 24/6/111880 doi:10.1067/mva.2001.111880
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documented the comparability of results between CAS and surgical management for restensosis after primary CEA. However, in the absence of randomized clinical trial procedures,5 we are currently unwilling to expand the use of CAS beyond these defined subgroups of patients.11 An additional concern about the CAS procedure has been the potential for development of in-stent restenosis.12,13 This complication has been observed after coronary stenting in 16% to 59% of cases,14-16 whereas in-stent restenosis after iliac stenting has been observed in 13% to 39% of reported series.17-19 In-stent restenosis after CAS has been reported in only 4% to 5% of cases (Table I)3,4,20,21; however, clinical follow-up has been relatively short, generally less than 12 months. The purpose of the current study is to determine the incidence of in-stent restenosis after CAS in our clinical series and to evaluate the utility of endovascular techniques for the management of in-stent restenosis. METHODS Patient population. Between September 1996 and May 2000, 50 CAS procedures were performed on 46 consecutive patients according to a protocol approved by the Institutional Review Board to investigate the feasibility of CAS. Twenty-six patients were men (57%), and 20 were women (43%) with a mean age of 69 ± 11 years. Symptomatic and asymptomatic high-grade stenoses (≥ 80%) were included in this protocol. Baseline clinical characteristics of the group are summarized in Table II. Of the 50 stenotic lesions, 40 (80%) were post-CEA restenoses, 9 (18%) were primary lesions in patients with critical two- or three-vessel coronary artery disease, and 1
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Table I. Incidence of in-stent restenosis after CAS
Diethrich et al3 Theron20 Yadav et al4 Wholey et al21
n
Restenosis (%)
Follow-up (mo)
110 93 126 2048
4.5 4. 4.9 4.8
8 12 6 6
(2%) was a stenosis that was complicating childhood cervical radiation therapy. Clinical protocol and follow-up. Clinical, angiographic, and procedural data were prospectively collected. Prior to and 24 hours after CAS, patients were examined by the vascular surgeon, interventionist, or, in some instances, an independent neurologist. All patients were followed up prospectively at 3- to 6-month intervals clinically and underwent duplex ultrasonography (DU). Restenotic lesions detected with DU were further evaluated with angiography for confirmation of the severity of stenosis. CAS protocol. CAS was performed as previously described12 (Fig 1). Patients were pretreated with aspirin (325 mg/d) for at least 2 days before the procedure and with either ticlopidine (250 mg twice daily) or clopidogrel (75 mg once daily) after a loading dose that was given the day of the procedure. Aspirin and one of the other two antiplatelet agents were continued for 4 weeks after CAS with aspirin therapy alone thereafter. Patients received intravenous sedation, and local anesthesia was achieved with infiltration of 1% lidocaine (Xylocaine). Venous access was secured in all patients, and a transvenous pacemaker was routinely available. Standard retrograde access was performed in the common femoral artery, and a 6F vascular sheath was inserted. Weight-adjusted heparin was administered (70 U/kg), and the activated clotting time was maintained at 225 to 250 seconds throughout the procedure. A 0.035-in guidewire (Wholey modified J, 175-cm; Mallinkrodt, St Louis, MO,) in a 5F Vitek or HN2 cerebral diagnostic catheter (Cook, Bloomington, Ind) was introduced for selective cannulation of the common carotid artery (CCA). Digital angiography was performed to confirm the severity of stenosis. Subsequently, the diagnostic catheter was exchanged over a 0.035-in exchangelength (260 cm) Amplatz Super Stiff guidewire (Meditech/Boston Scientific, Natick, Mass) for an 8F 100cm long sheath that was passed into the CCA. The stenosis was crossed with a 0.018-in Roadrunner extrasupport guidewire (Cook), and prestent dilatation was performed with low-profile 4 × 30-mm balloon catheters inflated to 8 atm, followed by stent deployment. Poststent dilatation was performed with 5- or 6-mm high-pressure balloons inflated to 12 atm. In the 46 patients, 50 stents were used during the carotid interventions. One patient underwent staged bilateral CAS procedures with Wallstents for postCEA restenoses, and three patients had use of a second stent (2 Wallstents and 1 Palmaz stent) for separate stenoses in the CCA. Of the 50 stents, 49 (98%) were self-
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Table II. Baseline clinical characteristics of the study group (N = 46)
Men Women Asymptomatic (> 80%) Symptomatic Hemispheric TIA Amaurosis fugax Global symptoms Diabetes Hypertension Smoker Hypercholesterolemia Coronary artery disease
n
%
26 20 28 18 6 2 10 15 39 23 23 25
57 43 61 39 13 4 22 33 85 50 50 54
expanding Wallstents, 8 × 20 mm and 10 × 20 mm (Meditech/Boston Scientific, Minneapolis, Minn), and 1 (2%) was a Palmaz P-154 stent (Johnson and Johnson Interventional Systems Co, Warren, NJ). On completion of the procedure, ipsilateral carotid and intracranial angiography was performed to assess technical success and to exclude distal cerebral embolization. Vascular sheaths were removed after the procedure, and femoral hemostasis was accomplished by means of a transcatheter closure device, Prostar XL (Perclose/Abbott, Redwood City, Calif). Imaging criteria and end points. Restenosis detected with DU was classified as moderate (50%-79%) and severe (≥ 80%). Quantitative angiographic analysis was performed on all arteries before and after CAS and for verification of restenosis detected with follow-up DU. An on-line software program of quantitative angiographic analysis was used (MDQM; MEDCON Telemedicine Technology, Inc, Livingston, NJ). With criteria from the North American Symptomatic Carotid Endarterectomy Trial,6 the degree of stenosis was determined by comparison of the least transverse diameter at the maximal stenosis with the reference diameter of the distal internal carotid artery once its walls became parallel. The minimal lumen diameter was measured after calibration of the system with the known diameter of the guiding catheter. Patients with high-grade restenosis (> 80%) revealed by DU underwent confirmatory angiography before reinterventions. RESULTS Demographics and outcome. CAS was performed on 50 carotid stenoses in 46 patients (Table II). There were 26 men (57%) and 20 women (43%). Of the 46 patients, 28 were asymptomatic (61%) and 18 were symptomatic (39%). Of the symptomatic group, six patients had hemispheric transient ischemic attacks (TIAs) without neurologic deficits, and two patients had amaurosis fugax. The remaining 10 patients complained of global symptoms, including severe lightheadedness, syncopal episodes, or both, but without any lateralizing neurologic deficits. After CAS, all patients were followed up clinically and
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A
B
C
D
Fig 1. A, Selective angiography in symptomatic patient presenting with single episode of amaurosis fugax 11 months after prior right CEA, demonstrating focal high-grade restenosis (arrow). B, Poststent deployment angioplasty resulted in technically satisfactory angiographic results (arrows refer to length of stent). C, In-stent restenosis was defined angiographically in two areas (arrows) in this patient 6 months after CAS. D, Angioplasties of both areas reduced lesions to < 30% residual stenoses (arrows), which have not recurred during a 14-month follow-up.
underwent DU at 3- to 6-month intervals during a mean follow-up time of 18 ± 10 months (range, 1-44 months). No minor or major strokes were observed in this series of 50 CAS procedures. Two TIAs were
observed during CAS. Each resolved spontaneously within minutes of its onset and without residual deficits. One patient (2.2%) died in this series. This 72-year-old woman had undergone a two-vessel coronary angio-
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plasty with stenting 2 days before CAS. Ten days after her discharge from the hospital, she died suddenly, presumably as a result of myocardial infarction. All other patients have remained asymptomatic. In-stent restenosis. Six in-stent restenoses were observed on follow-up DU: two (4%) were classified as moderate (50%-79%), and four (8%) were severe (> 80%). After evaluation with angiography, the two moderate stenoses were found to have < 50% stenosis and were not treated. The high-grade stenoses (> 80%) were confirmed in the other four patients, thus meeting the criterion for reintervention. Three of the treated in-stent restenoses developed in patients after CAS for post-CEA restenosis, whereas the fourth restenosis developed after an initial CAS procedure for radiation-induced stenosis. The clinical characteristics of patients with in-stent restenosis are outlined in Table III. Although these patients were asymptomatic, reintervention was recommended because of the severity of their restenosis (≥ 80%) and the presence of accompanying contralateral occlusion. In-stent restenosis was observed at a mean interval of 13 ± 7 months (range, 6-21 months) after the original CAS procedure. Three of the four restenoses were treated with angioplasty alone (Fig 2). The remaining patient was treated with angioplasty and restenting with a Palmaz stent. All four patients remained asymptomatic and without recurrent restenosis over a mean follow-up time of 10 ± 6 months (range, 1-14 months). DISCUSSION Prospective randomized clinical trials have confirmed the efficacy of CEA over optimal medical management alone for the treatment of symptomatic6-8 and asymptomatic9-10 patients with high-grade extracranial carotid stenoses. However, CAS has emerged as an alternative treatment modality, especially in high-risk patients. An endovascular approach may be better suited for the treatment of patients with restenotic lesions after CEA, with primary stenoses with high-risk medical comorbidities, or with radiation-induced stenoses. Although our group reported comparable results between CAS and surgical management of post-CEA restenoses, 12 surgical intervention has generally been associated with a higher rate of complications than those reported after primary CEA. Bartlett et al22 reported a 30-day stroke and death rate of 6.0%, whereas Das et al23 reported 4.6% and Treiman et al24 reported 3.5%. All noted increased risks of transient cranial nerve palsies. These results have stimulated interest in the use of CAS for post-CEA restenoses.1,12,25,26 Coronary stenting has been associated with significantly lower rates of angiographic and clinical restenosis than angioplasty alone.27,28 This salutary effect may be due to the stent’s ability to provide predictably larger arterial lumens.29 However, myointimal hyperplasia accompanies virtually every stent placement in the coronary, iliac, or carotid system, and some patients have hyperplasia of sufficient magnitude to cause flow-limiting restenosis.
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Table III. Clinical characteristics of the patients with instent restenosis (n = 4)
Men Women Asymptomatic (> 80%) Diabetes Hypertension Smoker Hypercholesterolemia Coronary artery disease
n
%
1 3 4 1 2 2 1 0
25 75 100 25 50 50 25 0
Restenosis has been reported to be as high as 59% after coronary angioplasty-stenting16 and 39% after iliac interventions.19 However, on the basis of collected clinical data from 24 centers, Wholey et al21 reported a rate of restenosis after CAS of only 4.8% (n = 2048) at a mean of 6 months of clinical follow-up. Diethrich et al3 defined a restenosis rate of 4.5% after 8 months of follow-up, whereas Yadav et al4 reported 4.9% at 6 months and Theron20 reported 4% at 12 months. The basis for this apparent lower incidence of in-stent restenosis in the carotid circulation as compared with the coronary and iliac vasculatures remains unknown. We investigated the incidence of in-stent restenosis after CAS in a high-risk surgical group for a follow-up interval of 18 ± 10 months (range, 1-44 months). We observed four patients (8.7%) with significant (≥ 80%) in-stent restenosis. Three of the patients were treated with angioplasty alone (Fig 2), and the fourth patient was treated with angioplasty and restenting. Although our series of 50 CAS procedures has been restricted to defined subgroups of patients,11 our cases of in-stent restenosis have been observed in patients after prior CEA or radiation therapy. Thus, our reported incidence of in-stent restenosis may be more reflective of CAS performed for post-CEA restenosis. Although myointimal hyperplasia with smooth muscle cell proliferation is the predominant mechanism leading to in-stent restenosis30 as well as the underlying mechanism for restenosis occurring within 2 to 3 years of CEA,22-24 stent implantation in a preexistent hyperplastic process may be associated with a higher incidence of in-stent restenosis than after CAS for primary stenosis. Currently, we recommend CAS for post-CEA restenosis, primary stenoses in high-risk patients, and radiationinduced stenosis. The 30-day stroke and death rate in our series was 2.2%. Although in-stent restenosis was detected in four (8%) of the 50 CAS procedures, treatment with angioplasty or angioplasty and re-stenting was effective and not associated with neurologic complications. None of these lesions has recurred during clinical or DU followup. All patients continue to be asymptomatic, and no further operative interventions have been performed in these post-CAS patients.
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B
A
Fig 2. A, Angiographic demonstration of focal in-stent restenosis developing at upper aspect of WallStent (arrow) 7 months after CAS. B, Treatment with angioplasty and placement of Palmaz stent produced a technically satisfactory angiographic result (notice that external carotid artery was occluded during a prior operative intervention; stenosis at proximal end of prior CEA site demonstrated no pressure gradient and was not treated).
REFERENCES 1. Theron J, Raymond J, Casasco A, Courtheoux F. Percutaneous angioplasty of atherosclerotic and postsurgical stenosis of carotid arteries. AJNR Am J Neuroradiol 1987;8:495-500. 2. Roubin GS, Yadav S, Iyer SS, Vitek J. Carotid stent-supported angioplasty: a neurovascular intervention to prevent stroke. Am J Cardiol 1996;78 Suppl 3A:8-12. 3. Diethrich EB, Ndiye M, Reid BD. Stenting in the carotid artery: initial experience in 110 patients. J Endovasc Surg 1996;3:42-62. 4. Yadav JS, Roubin GS, Iyer S, Vitek J, King P, Jordan WD, et al. Elective stenting of the extracranial carotid arteries. Circulation 1997;95:3 76-81. 5. Bettmann MA, Katzen BT, Whisnant J, Cochairs: Brant-Zawadzki M, Broderick JP, et al. Carotid stenting and angioplasty: a statement for healthcare professionals from the Councils on Cardiovascular Radiology, Stroke, Cardiothoracic and Vascular Surgery, Epidemiology and Prevention, and Clinical Cardiology, American Heart Association. Stroke 1998;29:336-48. 6. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991;325:445-53. 7. European Carotid Surgery Trialists’ Collaborative Group. MCR European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. Lancet 1991;337:1235-43. 8. Mayberg MR, Wilson SE, Yatsu F, VA Symptomatic Carotid Stenosis Group. Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. JAMA 1991;266:3289-94. 9. Hobson RW, Weiss DG, Fields WS, Goldstone J, Moore WS, Towne
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JB, et al. Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. N Engl J Med 1993;328:221-7. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid stenosis. JAMA 1995;273:1421-8. Veith FT, Amor M, Hobson RW, et al. Consensus panel on carotid angioplasty-stent. J Vasc Surg. In press 2000. Hobson RW, Goldstein JE, Jamil Z et al. Carotid restenosis: operative and endovascular management. J Vasc Surg 1999;29:228-38. O’Hara PJ. Carotid restenosis: operative and endovascular management [discussion]. J Vasc Surg 1999;29:236-7. Laham RJ, Carrozza JP, Berger C, et al. Long-term (4- to 6-year) outcome of Palmaz-Schatz stenting: paucity of late clinical stent-related problems. J Am Coll Cardiol 1996;28:820-6. Edelman ER, Rogers C. Hoop dreams: stent without restenosis. Circulation 1996;94:1199-202. Kastrati A, Schomig A, Elezi S, et al. Predictive factors of restenosis after coronary stent placement. J Am Coll Cardiol 1997;30: 1428-36. Cikrit DF, Gustafson PA, Dalsing MC, Harris VJ, Lalka SG, Sawchuk AP, et al. Long-term follow-up of the Palmaz stent for iliac occlusive disease. J Vasc Surg 1995;118:608-13. Becquemin JP, Allaire E, Qvarfordt P, Desgranges P, Kobeiter H, Melliere D. Surgical transluminal iliac angioplasty with selective stenting: long-term results assessed by means of duplex scanning. J Vasc Surg 1999;23:422-9. Sapoval MR, Chatellier G, Long AL, Rovani C, Pagny JY, Raynaud AC, et al. Self-expandable stents for the treatment of iliac artery obstructive lesions: long-term success and prognostic factors. AJR Am J Roentgenol 1996;165:1173-9.
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20. Theron JG. Carotid artery stenosis: treatment with protected balloon angioplasty and stent placement. Radiology 1996;201:627-36. 21. Wholey MH, Wholey M, Bergeron P, Diethrich EB, Henry M, Laborde JC, et al. Current global status of carotid artery stent placement. Cathet Cardiovasc Diagn 1998;44:1-6. 22. Barlett FF, Rapp JH, Goldstone J, Ehrenfeld WK, Stoney RJ. Recurrent carotid stenosis: operative strategy and late results. J Vasc Surg 1987;5:452-6. 23. Das MD, Hertzer NR, Ratliff NB, O’Hara PJ, Beven EG. Recurrent carotid stenosis: a five-year series of 65 operations. Ann Surg 1985;202:28-35. 24. Treiman GS, Jenkins JM, Edwards WH, Barlow W, Edwards WH, Martin RS, et al. The evolving surgical management of recurrent carotid stenosis. J Vasc Surg 1992;16:354-63. 25. Bergeron P, Chambran P, Benichou H, Alessandri C. Recurrent carotid disease: will stents be an alternative to surgery? J Endovasc Surg 1996;3:76-9. 26. Yadav JS, Roubin GS, King P, Iyer S, Vitek J. Angioplasty and stent-
Submitted Jun 12, 2000; accepted Sep 15, 2000.
DISCUSSION Dr Timothy M. Sullivan (Greenville, SC). Since my time is short and given Dr Porter’s previous comments, I’ll try and cut to the chase. First, Dr Hobson, given the relatively benign nature of recurrent stenosis following carotid endarterectomy, there are those who recommend treatment of these lesions only when they become symptomatic. Given a combined risk of stroke and death of 2.2% in your series, is it really reasonable to subject these patients, the majority of whom did not have hemispheric symptoms, to an experimental and unproven therapy? Second, as a vascular surgeon who performs carotid intervention, I’d like to know when to consider operation for my patients with multiple recurrences and when to consider reintervention? Third, the Wallstent has been shown to be a fairly efficient machine for inducing myointimal hyperplasia in other arterial beds, most notably the superficial femoral artery. Do you think your results would be better if you had used a different stent, and which stent are you currently using? Next, when considering interventional therapy for recurrent stenoses following endarterectomy, do you differentiate between early restenosis, which is likely myointimal and probably low risk for intervention, and late restenosis, which is atherosclerotic and may be higher risk for intervention? Finally, given the fairly low rate of restenosis that your group and others have documented, and with the advent of cerebral protection devices, the question that begs to be asked is, what are your predictions for the fate of carotid endarterectomy over the coming decade? Although Dr Hobson has reported reasonable results for the interventional treatment of carotid restenoses, it is important that these results not be extrapolated to angioplasty for de novo carotid stenoses. These are, however, important data. It is even more important that vascular surgeons be involved in the review of this new technology so that hard, peer-reviewed, and honest data are utilized to dictate medical care for our patients, rather than reports of anecdotal experiences from investigators who may have a personal and financial interest in the success of this new procedure. Thank you. Dr Robert W. Hobson II. Thanks very much, Dr Sullivan. Those are excellent questions. First of all, we know that the restenotic lesion has a low neurological event rate. However, data on restenoses ≥ 80% and their possible progression to occlusion are not well defined. As a result, we selected the 80% diameter-reducing stenosis as the threshold for intervention. I recognize that this is controversial, and some of you may not choose intervention in these cases. However, this became part of our clinical protocol. With regard to reoperations for restenosis, we have not found that necessary during the last 4 years. Angioplasty and stenting
appear to be a reasonable alternative for initial cases of restenosis. The Wallstent is not the stent of choice in my opinion. If you remember the first case I presented with a focal restenosis, we used a 40-mm stent, which resulted in a lengthy segment of normal internal carotid being covered with the stainless steel stent. Ultimately, if recurrent restenosis develops, operation with a venous interposition graft may be required. However, we have not yet encountered such a case. The newer nitinol technology will offer us advantages in more precise placement of the stent and probably with equivalent or perhaps even lower in-stent restenosis rates. Early restenotic lesions due to myointimal hyperplasia (within 3 years of CEA) were selected preferentially in this series because of an anticipated lower incidence of embolization during CAS. For stenoses occurring beyond the 3-year interval, selection would be based in part on the results of duplex ultrasonography. For lesions comparable to primary atherosclerotic plaques, reoperation should be considered rather than CAS, until cerebral protection devices are available. As far as our reported incidence of in-stent restenosis and the ultimate decision about using this procedure in primary stenosis patients, clearly, a need exists for randomized clinical trial methodology. Our reported case series, performed over the last 4 years, accounted for less than 8% of our procedures in patients with cerebrovascular insufficiency. Restenosis is an example of one of the subsets of patients that the American Heart Association’s Consensus Panel has suggested as reasonable for angioplasty and stenting. But none of us will be prepared to move away from the gold standard of carotid endarterectomy based on retrospective evidence. Until we have data from randomized, prospective clinical trials, endarterectomy will remain the mainstay of treatment of patients with symptomatic and asymptomatic extracranial carotid occlusive disease. Thank you. Dr. Kevin G. Burnand (London, United Kingdom). Dr Hobson, thank you very much for that series. Are you actually suggesting to us that the carotid is some sort of privileged site in terms of the restenosis rate? Are you surprised at the difference in restenosis rates from stents compared from the angioplasty series that have been recorded? Dr Hobson. I was surprised. Given the incidence of restenosis after angioplasty-stenting in the coronary circulation and the iliac arteries, many of my partners predicted that we’d be intervening on in-stent restenosis cases by percutaneous techniques or perhaps skull-based operations. However, our results have suggested a much lower incidence of recurrent restenosis following CAS. As emphasized by Dr Sullivan, the earlier lesions are myointimal hyperplasia. It is possible that the carotid artery’s high-flow rate and low cerebrovascular resistance may result in an incidence of myointimal hyperplasia that is lower than associated with other vasculatures.
27.
28.
29.
30.
ing for restenosis after carotid endarterectomy: initial experience. Stroke 1996;27:2075-9. Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N Engl J Med 1994;331:496-501. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heydrickx G, et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med 1994;331:489-95. Kuntz RE, Gibson CM, Nobuyoshi M, Baim DS. Generalized model of restenosis after conventional balloon angioplasty, stenting and directional atherectomy. J Am Coll Cardiol 1993;21:15-25. Mintz GS, Popma JJ, Hong MK, et al. Intravascular ultrasound to discern device-specific effects and mechanisms of restenosis. Am J Cardiol 1996;78 Suppl 3A:18-22.
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Dr William D. Turnipseed (Madison, Wis). We’re all aware of the fact that whether you treat carotid stenosis by primary stenting or carotid surgery, hyperplastic recurrence is a fact of life. My concern is when there are tertiary and/or quartenary recurrences that are often encountered, after re-endarterectomy and/or patch placement with the same misery of recurrent stenosis thereafter. It would seem at first blush that stenting would be an attractive way to deal with this kind of recurrent lesion. From bad personal experience, I would raise the question of whether there are relative contraindications for using stents in patients who have previous prosthetic patch placement for recurrent stenosis. We have had two experiences, one in the iliac and one in the carotid artery, where the patches disrupted late after the initial successful angioplasty. These became infected. Let me tell you, salvage procedures for an infected mycotic aneurysm with a stent in place are very challenging operations. Dr Hobson. Bill, thank you for your comments. I’ll take your word that it is a challenging operation. However, with careful sizing of the stent, this is the preferred procedure for postendarterectomy restenosis. It is associated with a low complication rate. If in-stent restenosis does occur, at least in our series, subsequent endovascular management is an option that appears to be reasonable and safe. It
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would also appear that the presence of a synthetic patch is not a contraindication to the procedure. Dr George Andros (Encino, Calif). I’m not going to comment on the appropriateness of these procedures or the procedure itself. And we scarcely need anybody else in the room to comment on the controversies, as John is up there. But we certainly have to take this as a landmark paper. To my recollection this is the first paper that I know of in this Society—and it’s particularly appropriate that it’s given by the president-elect—in which all the endoluminal procedures were done by a vascular surgeon. And I think that signifies an end to when we’re going to see vascular surgeons stand up here and present the work done by their interventional radiologists where they might not even have been in town when the cases were done and they weren’t really sure what kind of balloon was used in-stent. So I congratulate you, Bob. I think that you’ve shown us the future, and it’s that vascular surgeons have to present their own endovascular work. Dr Hobson. Thank you, George. We did collaborate with colleagues in cardiology. However, I scrubbed on every case, and our fellow in vascular surgery has been an important part of this program. I agree that it is time for vascular surgery to present its own results on endovascular procedures. Thank you very much.
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