Published online before print March 27, 2003, doi: 10.1161/01.STR.0000065106.12772.29
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(Stroke. 2003;34:834.)
© 2003 American Heart Association, Inc.
Letters to the Editor |
Carotid Angioplasty and Stenting in High-Risk Patients With Severe Symptomatic Carotid Stenosis
Section of Vascular Surgery, Department of Medical & Surgical Sciences, University of Padua, Padua, Italy
To the Editor:
In a recent article, Fox et al1 claim to have demonstrated the beneficial effect of a carotid angioplasty and stenting (CAS) procedure performed in a consecutive series of "poor surgical candidates" with severe symptomatic carotid stenosis by comparison with the outcome observed in medically-treated patients in the North American Symptomatic Carotid Endarterectomy Trial (NASCET).2 In our opinion, the conclusions drawn by the authors are misleading for the following reasons.
First, the authors present a data analysis on a case series, for which the reader is simply informed of the fate of a relatively small sample of patients (n=42) (level V evidence).3 This type of retrospective study can hardly be used to dispute the results of a prospective, randomized trial, such as the NASCET,2 designed to test a specific hypothesis (level I evidence): this defies logic.
Second, the authors acknowledge that most, if not all, of the patients in their series would have been excluded from NASCET for specific reasons - namely, medical risk factors (9.5%), angiographic risk factors (47.6%), restenosis after carotid endarterectomy (CEA) (40.4%), and stenosis after neck irradiation (9.5%)—and that "it would have been reasonable to assume that these patients would have had a similar natural history risk of stroke if left untreated as the NASCET medical treated patients". This assumption is a biased conjecture since the NASCET medically-treated patients form a carefully-selected group that met the same inclusion criteria as the surgically-treated patients. Indeed, the relatively strict inclusion/exclusion criteria in the most influential surgical trials2,4 rejected many patients who represent an important share of the general patient population with cerebrovascular disease. None of these trials designed their criteria as risk classification standards for carotid disease treatment, however; they were simply for the purpose of ensuring a good-quality data set to answer the questions their study had posed.
A recent consensus statement emphasized that CAS should be restricted to limited subgroups of patients, whereas the "gold standard" CEA is still preferable for the management of most patients with occlusive carotid disease.5 Even more recently, a multidisciplinary panel concluded that certain subgroups of patients, namely high-risk symptomatic patients or those unfit for surgery, should currently be considered for CAS.6 Lacking a specific definition of "high-risk" and "unfit for surgery", there is a general tendency to identify high-risk patients as those who do not meet the inclusion criteria for multicenter randomized studies,2,4 or who have significant medical co-morbidities, or specific anatomical features associated with a worse outcome6,7 Since the term "high-risk" does not imply that CEA is "absolutely contraindicated" in such patients, we, like other investigators,8,9 have recently focused on this population subset, comparing the peri-operative outcome of CEA between patients who were high-risk and those who were not (E. Ballotta, MD, et al, unpublished data, 2002). Over a 54-month period, 392 consecutive CEAs were performed in 363 patients: all CEAs involved carotid eversion endarterectomy with the patient under deep general anesthesia and cerebral protection involving continuous electroencephalographic monitoring for selective shunting. A high-risk patient subset (n =126, 34.7%) was defined by the presence of a severe medical co-morbidity (ie, cardiac dysfunction, pulmonary dysfunction, renal insufficiency) and/or particular anatomical features (ie, contralateral carotid occlusion, ipsilateral carotid restenosis after CEA and "high" carotid bifurcation). Of the 126 CEAs, 96 (76.2%) were performed for symptomatic severe carotid lesions (stenosis greater than 70%, computed by the NASCET method). Endpoints of the study were perioperative stroke, cardiac complication or death. Overall, there were three ischemic strokes (0.7%) and four cardiac complications (1%). None of the patients died. The stroke rate in the high-risk group was comparable with that of the non-high-risk group (0.8% versus 0.7%). The only adverse neurological event, albeit minor, that developed in the high-risk group was probably related to hemodynamic reasons since the stroke was ipsilateral to the hemisphere of the occluded contralateral ICA: the endarterectomized vessel was found patent, with no technical defects, at postoperative angiography. Similarly, none of the clinical conditions or particular anatomic features considered in our study emerged as predictors of neurological events. Age and gender had no significant impact on stroke incidence. Although no asymptomatic patients developed a perioperative stroke, the presence of symptoms did not adversely affect the stroke rate. These findings correlated closely with two recently-published reports dealing specifically with the high-risk patient population,8,9 showing that high-risk patients can undergo CEA with a stroke rate equivalent to that of non-high-risk patients.
The alarming 9.5% peri-procedural stroke rate reported by Fox et al in their high-risk patient population consequently seems unacceptable when compared with the 0.8% (1/126) peri-operative stroke incidence emerging from our own study, or the 4.4% (3/68) and the 2.0% (2/98) recorded in similar case series after CEA8,9 or the 3.6% (1/28) peri-procedural stroke rate described in other CAS experiences dealing with NASCET-ineligible patients.10 Moreover, the claim that a comparable peri-procedural disabling stroke rate (9.9%) was observed in the CAS group of the only completed randomized clinical trial comparing CEA with CAS, ie, the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS),11 is a lame excuse. Indeed, the CAVATAS trial showed similar major risks and effectiveness for surgical and stenting procedures, yielding peri-procedural stroke and death rates of about 10% in each group - much higher than those of the large CEA trials2,4 on which treatment recommendations are based. In conclusion, the defining a patient as a "poor candidate for surgery" should not be considered per se a valid reason for preferring CAS to CEA, especially when the peri-procedural stroke rate is questionable.
References
- Fox DJ, Moran CJ, Cross DT III, Grubb RL Jr, Rich KM, Chicoine MR, Dacey RG Jr, Derdeyn CP. Long-term outcome after angioplasty for symptomatic extracranial carotid stenosis in poor surgical candidates. Stroke. 2002; 33: 2877–2880.
[Abstract/Free Full Text] - 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: 445–453.[Abstract]
- Cook DJ, Guyatt GH, Laupacis A, Sackett DL, Goldberg RJ. Clinical recommendations using levels of evidence for antithrombotic agents. Chest. 1995; 108 (suppl 4): 227S–230S.[Medline] [Order article via Infotrieve]
- European Carotid Surgery Trialists Collaborators Group, MRC European Carotid Surgery Trial. Interim results for symptomatic patients with severe (70–99%) or with mild (0–29%) carotid stenosis. Lancet. 1991; 337: 1235–1243.[CrossRef][Medline] [Order article via Infotrieve]
- Bettmann MA, Katzen BT, Whisnant J, Brant-Zawadzki M, Broderick JP, Furlan AJ, Hershey LA, Howard V, Kuntz R, Loftus CM, 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: 336–338.
[Free Full Text] - Veith FJ, Amor M, Ohki T, Beebe HG, Bell PRF, Bolia A, Bergeron P, Connors JJ III, Diethrich EB, Ferguson RDG, et al. Current status of carotid bifurcation angioplasty and stenting based on a consensus of opinion leaders. J Vasc Surg. 2001; 33: S111–S116.[CrossRef][Medline] [Order article via Infotrieve]
- Dangas G, Laird JR Jr, Mehran R, Satler LF, Lansky AJ, Mintz G, Monsein LH, Laureno R, Leon MB. Carotid artery stenting in patients with high-risk anatomy for carotid endarterectomy. J Endovasc Ther. 2001; 8: 39–43.[Medline] [Order article via Infotrieve]
- Lepore MR Jr, Sternbergh WC III, Salartash K, Tonnessen B, Money SR. Influence of NASCET/ACAS trial eligibility on outcome after carotid endarterectomy. J Vasc Surg. 2001; 34: 581–586.[CrossRef][Medline] [Order article via Infotrieve]
- Jordan WD, Alcocer F, Wirthlin DJ, Fisher WS, Warren JA, McDowell HA, Withley WD. High-risk carotid endarterectomy: challenges for carotid stent protocols. J Vasc Surg. 2002; 35: 16–22.[Medline] [Order article via Infotrieve]
- Malek AM, Higashida RT, Phatouros CC, Lempert TE, Meyers PM, Smith WS, Dowd CF, Halbach VV. Stent angioplasty for cervical carotid artery stenosis in high-risk symptomatic NASCET-ineligible patients. Stroke. 2000; 31: 3029–3033.
[Abstract/Free Full Text] - CAVATAS Investigators. Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomised trial. Lancet. 2001; 357: 1729–1737.Commentary 1722–1723.[CrossRef][Medline] [Order article via Infotrieve]
Interventional Neuroradiology Services, Mallinckrodt Institute of Radiology and the Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri
Response
Ballotta et al, have made serious errors in their reading of our article. We did not suggest or imply that angioplasty and stenting should be preferred over endarterectomy. Rather, we concluded that angioplasty and stenting was probably better than medical treatment for a very selected group of symptomatic patients that were poor surgical candidates.
We treated 42 patients with severe stenosis of a carotid artery and recent ischemic cerebral symptoms with angioplasty and stenting. All our patients were referred for endovascular treatment after evaluation by experienced surgeons. Many had lesions that were not surgically accessible. Most also had multiple medical co-morbidities. Our overall complication rate was higher than in some reported retrospective series but in the range reported in several reported prospective series in similar patients, as we discussed in our article. The complication rate we reported includes early as well as recent data, is improving over time with operators’ experience, and is expected to improve further as protection devices are incorporated into practice. The purpose of this study was not to compare complication rates of angioplasty and stenting with endarterectomy, but rather to examine long-term stroke risk after angioplasty and stenting and to compare it to data available from historical controls. The most important observation was that no patient in this study had a stroke during follow-up.
We consider carotid endarterectomy to be the standard of care for patients with symptomatic carotid artery stenosis greater than 70%. The data from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) are compelling: carotid endarterectomy provides a substantial reduction in the risk of stroke at 2 years when compared with medical treatment (aspirin). Subsequent analyses have confirmed the durability of this procedure. Our data were not used to dispute the results of NASCET in any manner.
As stated above, as well as repeatedly in our article, the question that we sought to answer was whether angioplasty and stenting was better than medical treatment alone. In our opinion, the best natural history data available was the medical treatment arm of NASCET. These patients were similar to our cohort in baseline characteristics and stroke risk factors. They shared the key inclusion criteria of a high-grade stenosis and recent symptoms. The 2-year risk of stroke in this group was 29%, much higher than the 9% we observed in our cohort study. We explicitly recognized that this analysis provides a poor level of evidence. Consequently we referred to our data as preliminary and tempered our conclusions.
We stand by our conclusion and reiterate it here for the benefit of Ballotta et al: in the absence of data from randomized clinical trials, our preliminary data suggest that angioplasty and stenting are better than medical treatment for symptomatic patients with severe carotid stenosis who are poor candidates for surgery.
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