Carotid revascularization for the prevention of neurovascular events is somewhat controversial in general. Carotid stenting, an investigational technique for carotid revascularization, is even more controversial. Nonetheless, this new technique demands careful consideration, particularly with the evolution of distal protection devices such as GuardWireTM, an unlabeled use of a commercial product, which the authors discuss. Drs. Salloum and Campbell have combined to provide some insights into this interesting evolving technique. Please welcome Drs. Salloum and Campbell to Cyberounds^®!

-- Richard W. Smalling, M.D., Ph.D., Cardiovascular Editor

It is estimated that, each year, 25% of the 500,000 strokes in the United States are caused by atherosclerotic carotid artery disease. The conclusions of multiple clinical trials have helped to forge a consensus regarding the standard of care, which revolves around two main modalities of treatment: pharmacologic therapy and carotid endarterectomy. The indications for carotid endarterectomy in symptomatic patients with a surgeon whose combined surgical mortality and morbidity rate is less than 6% are:(1)

Class I: One or more transient ischemic attack(s) (TIA) within the past 6 months and carotid artery stenosis >70% by diameter.

Class II: TIA within 6 months and a carotid artery stenosis 50% to 69%; progressive stroke and a stenosis >70%; mild or moderate stroke in the past 6 months and a stenosis 50% to 69%; or TIA and an ipsilateral carotid stenosis >70% combined with required coronary bypass grafting.

Class III: TIAs or mild stroke with a stenosis <50%, TIAs with a stenosis <70% combined with coronary artery grafting, or symptomatic, acute carotid thrombosis.

Class IV: Moderate stroke or single TIA with stenosis <50%, not on aspirin; global ischemic symptoms with stenosis <50%; acute dissection, asymptomatic on heparin.

Nevertheless, the advancements in endovascular procedures in general and stenting in particular have tempted clinicians to tackle obstructive carotid artery disease using the percutaneous transluminal approach.

The "Gold Standard"

The results of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) have shown that, at 90 days, the mortality rate of carotid endarterectomy in symptomatic patients with greater than 70% narrowing in their internal carotid artery diameter is 1.1%. At the same time of follow up, the rate of disabling and nondisabling stroke is 0.9% and 4.5%, respectively, while cranial nerve palsies occur in 8.6% of cases.(2) The Asymptomatic Carotid Atherosclerosis Study (ACAS) investigators reported a total event rate of 2.6%. Their conclusion was that, so long as the complication rate remains below 3%, carotid endarterectomy is beneficial for asymptomatic patients with at least 60% reduction in diameter of their internal carotid artery.(3) The conclusion of this trial provided the clinician with another indication for endarterectomy in the difficult situation of the asymptomatic patient who is accidentally discovered to have significant carotid occlusive disease.

Endarterectomy, however, is limited to the cervical portion of the carotid vessel: above the clavicle yet not cephalad to the C2 or C3 level. Furthermore, the above results were obtained in the hands of skilled surgeons operating on a select group of patients, reflecting a population thought to have low operative morbidity and mortality.

The "Challenger"

A reasonably recent survey of major interventional centers in North and South America, in addition to Europe, indicated that, as of September 1999, 4,757 patients underwent endovascular carotid artery stenting (see Figure 1).

Figure 1. Internal Carotid Artery Stenting; Before and After the Procedure.

The overall mortality rate was 0.86% at thirty days. Major strokes occurred in 1.49% of patients. The combined rates of death, major and minor stroke were 5.07%.(4) A more recent series by Shawl and his co-workers reported the results of carotid artery stenting in 170 patients. These patients, in general, exhibited a higher surgical risk than those patients involved in the above survey or those included in NASCET or ACAS. In fact, 76% of them would have been excluded from either of the surgical trials and 31% of them were actually referred by vascular surgeons. The overall death and stroke rate at 30 days was 2.9%. At 19 months, death rate was 5.2% although none of the deaths was attributable to a neurologic cause. The stroke rate at 19 months was 4.7%.(5) Other investigators have also reported similar results.

Comparison

Considering the above data, many feel that carotid stenting has a role to play in the treatment of carotid disease. At first glance, the figures quoting complication rates may seem greater in carotid artery stenting as compared to carotid endarterectomy; nonetheless, a more detailed examination of these data yields a different conclusion.

Carotid endarterectomy data are obtained from clinical trials involving major centers and a select population of patients that has been sieved through rigorous exclusion criteria. Carotid artery stenting data, on the other hand, derive from patient series that are usually sicker and are at a disadvantage with an increased risk of mortality and morbidity.

The rate of restenosis in carotid stenting, as reported by many series now, does not appear to represent a major issue, unlike the case in the coronary vessels. Restenosis rates range around 4.8% at six months, compared to recurrence rates of 12.7% to 20.4% at 60 months after endarterectomy as per ACAS follow-up reports.(6) These high rates of recurrence after surgery usually occur if the surgical technique does not involve the use of a vein patch.

A shorter hospital stay, mean of 1.86 days post procedure, according to Shawl et al.(5) is undoubtedly an advantage in carotid stenting. Furthermore, stenting eliminates the need for an incision, hence eliminating surgical wound complications. The occurrence of cranial nerve palsy, relatively common in endarterectomy procedures, has not yet been reported as a complication of percutaneous carotid procedures.

Discussion

Carotid artery stenting is still a field in its infancy. The technology employed was initially devised for coronary or peripheral vascular procedures. Catheters and stents that are more adapted to the carotid vessels, together with the use of distal embolization protection devices and the growing experience in carotid stenting techniques, will probably result in significantly fewer complications. One such protection device is the GuardWire^TM system by PercuSurge ^TM (Figure 2).

Figure 2. The GuardWire Distal Protection Device by PercuSurge.

Click to see full sized image

Briefly, it consists of a special guide wire equipped with an inflatable balloon at its tip. After crossing the lesion, the distal protective balloon is inflated, thus occluding the vessel distal to the lesion. The stent is then delivered over the wire in the usual manner. Before deflating the distal balloon, a special suction catheter is introduced and the debris is aspirated and disposed of. The wire balloon is finally deflated and the wire withdrawn.

The preliminary clinical data on the application of the GuardWire^TM system in the CAFE study are promising. Seventy-five patients were treated, 56% of whom had symptomatic disease and 31% had severe contralateral carotid disease. In addition, 36% of patients had angina and 28% had suffered cerebrovascular accidents. Procedural success was achieved in all cases. No strokes were recorded and only one patient suffered from a wire-related dissection. Patients tolerated a mean balloon occlusion time of 15.3 + 5.5 min. Data from the PercuSurge^TM global registry are even more impressive. Of 463 procedures performed in 19 institutions, only 7 (1.5%) were complicated by death or stroke.

Use of pharmacologic agents that are known to improve outcome in coronary interventions, namely glycoprotein IIb/IIIa inhibitors, may constitute another advance. One small patient series has already reported improved safety and feasibility of their use in carotid stenting.(7)

Even in this early stage of carotid stenting, several categories of patients seem to benefit from stenting in experienced centers. Patients with carotid stenosis post endarterectomy have pathology that differs substantially from that of atherosclerotic disease. The low propensity for distal embolization and the high-risk profile of redo surgery make stenting an attractive alternative in this situation. Similar circumstances make carotid stenting more beneficial in those patients who suffer from carotid occlusive disease and have a history of radical neck dissection or neck irradiation. Fibromuscular dysplasia patients are also well suited for carotid artery stenting because of its low procedural complication rate.

Additional ideal candidates for carotid artery stenting are those patients who have severe disease located beyond the vascular surgeon's reach. These patients are at the mercy of their atherosclerotic plaque and all they can be offered otherwise is medical therapy. No formal study comparing carotid stenting to medical therapy has, to our knowledge, been conducted. NASCET and ACAS have, nonetheless, established guidelines for endarterectomy based on better patient outcome. Medical therapy has also been compared to surgical treatment of carotid artery disease, with the results echoing those of the above named trials.(8) Since the risk benefit ratio of carotid stenting closely mirrors that of endarterectomy, stenting the surgically inaccessible lesion seems to be in the best interest of the patient.

The independent predictors of poor outcome in endarterectomy are very different from those in carotid artery stenting. As far as carotid endarterectomy is concerned, these predictors include contralateral carotid occlusion, previous ipsilateral carotid endarterectomy, and combined coronary and carotid artery disease. In carotid artery stenting, symptomatic lesions, advanced age, and long or multiple stenoses independently predict procedural stroke.(9)

This difference in the characteristics of patients at highest risk for each respective procedure, in essence, allows the opportunity for endarterectomy and stenting to assume complementary roles. Hence, one approach to carotid artery disease would not necessarily interdict the other. A given patient whose complex medical profile and severe contralateral disease puts him in an unfavorable position for endarterectomy is probably better served by an experienced interventional physician. Another patient, elderly but relatively free of comorbidities and suffering from a complex and critical carotid lesion, probably requires a competent vascular surgeon.

Table 1. Independent Predictors of Poor Procedural Outcome.

Carotid Endarterectomy	Carotid Stenting
Contralateral carotid disease	Advanced age
Concomitant coronary disease	Symptomatic lesions
Previous carotid surgery	Long, complex, lesions

The importance of prompt restoration of blood flow and the well-recognized beneficial effects of thrombolytic therapy in acute stroke suggest a possibly important role for percutaneous intervention and carotid stenting in the setting of acute stroke. The current availability of qualified interventional teams that respond quickly and appropriately to acute myocardial infarction cannot but facilitate the creation of acute stroke response systems. At present, literature describing the outcome of percutaneous intervention and stenting in the setting of acute stroke is lacking. Future trials may lead to the establishment of stenting as standard of care in acute stroke resulting from carotid artery occlusion. Nonetheless, it is imperative to underline the higher risk profile of carotid stenting in this context. An active plaque and a setting of emergency procedure weigh heavily toward the development of a higher rate of complication than that quoted in elective intervention series.

Conclusion

The answer to our original question at this moment in time is by no means complete and certain. Ongoing clinical trials, comparing carotid endarterectomy to carotid stenting (Carotid Revascularization Endarterectomy versus Stent Trial, CREST) will probably yield a keener insight, thus allowing for a more definite answer. At this point, it appears almost certain that stenting will play an ongoing and growing role in the management of patients with carotid disease. In due time, this role will be better defined and widely applied. At present, carotid stenting must be considered an investigational procedure pending the outcomes of randomized trials, at least in the United States.