Carotid Angioplasty and Stenting With and Without Cerebral Protection
Clinical Alert From the Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S) Trial
Background and Purpose— Whether cerebral protection during carotid angioplasty and stenting (CAS) is associated with a lower risk of periprocedural stroke or death remains to be established. We report on 80 patients randomized in the CAS arm of the Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis trial comparing CAS (with or without cerebral protection) with carotid surgery in patients with recently symptomatic, severe carotid stenosis.
Summary of Report— The Safety Committee recommended stopping unprotected CAS, because the 30-day rate of stroke was 3.9 (0.9 to 16.7) times higher than that of CAS with cerebral protection (4/15 versus 5/58).
Conclusion— Although this result was not based on a randomized comparison of unprotected versus protected CAS, it suggests that the use of cerebral protection devices during CAS reduces periprocedural strokes.
In the past few years, evidence has accumulated that carotid angioplasty and stenting (CAS) might become an alternative to carotid endarterectomy1 for the treatment of patients with high-grade symptomatic carotid artery disease. Randomized clinical trials are in progress to compare these techniques. In order to reduce embolization of plaque fragments to the brain during CAS, cerebral protection devices have been developed, but it remains to be established whether these devices modify the risk of periprocedural complications.
Using data from the ongoing Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis (EVA-3S) trial, we report evidence that CAS with a cerebral protection device may be safer than CAS without cerebral protection.
EVA-3S is a multicenter, randomized, open, assessor-blind, non-inferiority study, with national research organization funding. The primary objective of this study is to evaluate whether CAS (with or without cerebral protection) is as safe and effective as carotid surgery as regards (1) the risk of stroke and death within 30 days of the procedure and (2) the long-term risk of ipsilateral carotid territory stroke, in patients with recently symptomatic, severe (≥70% NASCET) carotid stenosis. To join the study, each center must comprise a neurologist, an interventionalist, and a vascular surgeon. The interventionalist must document at least 12 cases of carotid See Editorial Comment, page e20 angioplasty and stenting or at least 5 cases of carotid angioplasty and stenting and 30 cases of endovascular treatment of other supra-aortic trunks. In centers in which the local interventionalist does not meet full requirement, angioplasty is performed under the responsibility of a tutor from another center, until he/she becomes self-sufficient, according to predefined criteria. Carotid angioplasty consists of primary stenting with or without use of cerebral protection. Any device can be used in EVA-3S provided that (1) the device is approved by the technical committee of the study and (2) the interventionalist can document at least 2 cases of patients treated with this device outside the trial. Patients must receive aspirin (100 to 300 mg daily) and either ticlopidine (250 mg twice daily) or clopidogrel (75 mg daily) for 3 days before and for 1 month after the procedure. Heparin is given during the procedure.
Patients are followed-up by the study neurologist at 1 month, 6 months, and every 6 months thereafter for 2 to 4 years. All outcome events are reviewed blindly by a Clinical Event Adjudication Committee. A major stroke is defined as a stroke that increases the modified Rankin Scale to 3 or more, 1 month after the event.
On January 30, 2003, the safety committee of EVA-3S recommended to stop unprotected CAS. At that time, 80 patients had been randomized in the CAS arm of the trial. The procedure could not be performed in 6 (7.5%) patients because of catheterization difficulties (CAS failure); these patients were subsequently treated by surgery. One patient had a stroke before planned angioplasty. CAS was performed in 73 patients, using a femoral (n=71), radial (n=1), or carotid (n=1) route. Cerebral protection devices were used in 58 (79.5%) patients. Except for a younger age of patients treated with cerebral protection, no significant difference was found between patients with or without cerebral protection (Table 1).
Twelve events were reported: 1 minor stroke after randomization but before procedure, 1 minor stroke during a failed procedure, and 9 strokes (3 major strokes) and 1 sudden death within 30 days of the 73 completed procedures. The overall combined stroke and death rate was 15.0% (95% CI, 8.0% to 24.7%) and that of major stroke and death was 5.0% (95% CI, 1.4% to 12.3%).
Table 2 shows the numbers of strokes and deaths within 30 days of the 73 completed procedures with and without cerebral protection. The 4 events in patients without cerebral protection occurred in 3 different centers, and the 6 events in patients with cerebral protection occurred in 5 different centers. Crude and age-adjusted odds ratios were all >2.5, although the lower limits of the confidence intervals were compatible with an absence of difference. As regards stroke, unprotected CAS was associated with a number needed to harm of 6.
In the first 80 patients randomized to the CAS arm of the EVA-3S trial, the overall stroke and death rate within 30 days was 15.0% (95% CI, 8.0% to 24.7%). Most of these strokes were nondisabling strokes, giving a combined major stroke and death rate of 5% (95% CI, 1.4% to 12.3%). While several single-center studies on CAS have been published,2,3 there is only a single completed prospective multicenter trial (Carotid and Vertebral Artery Transluminal Angioplasty Study [CAVATAS])4 to which we can compare our results. The rates of death or any stroke (minor strokes lasting <7 days were excluded) or death within 30 days was 10% in 251 patients randomly assigned to endovascular treatment, whereas the rate of disabling stroke (equivalent of modified Rankin grade ≥3) or death was 6%. Most patients (77%) underwent carotid angioplasty without stenting, and no procedure was performed with cerebral protection devices. The rate of technical success was 89%, similar to that found in our study (92.5%).
In our study, the risk of any stroke within 30 days of unprotected CAS was about 3 times that of patients treated with cerebral protection. Based on these data, the Safety Committee recommended stopping unprotected CAS, although the lower limits of the confidence intervals were compatible with an absence of difference. It should be stressed that our study was not designed to randomly compare CAS with and without cerebral protection and that the number of events is small. A center effect is unlikely to explain these results, since the 10 events occurred in 8 different centers. A learning effect is also unlikely to explain the different complications rates, since protected CAS is a more complex technique than unprotected CAS. Our findings are consistent with a systematic review of observational studies, in which the 30-day stroke and death rate in both symptomatic and asymptomatic patients was 1.8% in 896 patients treated with protection devices compared with 5.5% in 2537 patients treated without protection devices.5
Our results, in keeping with uncontrolled studies, suggest that CAS with cerebral protection may be safer than unprotected CAS. Further data from ongoing randomized clinical trials are awaited to confirm this finding.
Writing Committee: J.L. Mas, G. Chatellier, B. Beyssen. Scientific Committee: J.L. Mas, G. Chatellier, A. Branchereau, J.P. Becquemin, J.F. Bonneville, D. Crochet, J.C. Gaux, V. Larrue, D. Leys, J. Watelet. Clinical Event Validation Committee: T. Moulin, S. Bracard, M. Hommel, J.L. Magne, F. Mounier-Vehier. Interventional Techniques and Surgery Committee: B. Beyssen, J.F. Bonneville, L. Boyer, J.P. Favre, M. Giroud, K. Hassen-Kodja, J.B. Ricco. Imaging Committee: J.P. Pruvo, J.F. Meder, C. Arquizan, F. Becker, F. Cattin, J.M. Debray, J.M. Jausseran, A. Long, P.J. Touboul. Safety Committee: M. Lièvre, J.P. Beregi, J. Bogousslavsky, M. Testart.
The complete list of investigators and centers can be found at http://eva3s.hegp.bhdc.jussieu.fr.
This work was funded by Programme Hospitalier de Recherche Clinique of the French Ministry of Health (AOM 97066), Assistance Publique des Hôpitaux de Paris.
A list of contributors from the EVA-3S Investigators appears in the Appendix.
- Received July 21, 2003.
- Revision received September 18, 2003.
- Accepted September 23, 2003.