Carotid and Cerebrovascular Intervention

Carotid Bifurcation Atherosclerosis and Stroke

The carotid bifurcation has a remarkable predilection for the development of atherosclerosis, which is typically located at the origin of the internal carotid artery (ICA) ( Fig. 46.2 ). This plaque is similar to that found at other sites throughout the arterial system in that it contains a dense cap of connective tissue with embedded smooth muscle cells and an underlying core of lipid and necrotic debris. Histologic studies of plaque from the carotid bifurcation of symptomatic and asymptomatic individuals have revealed features associated with the development of symptoms that are similar to those associated with plaque vulnerability in the coronary circulation: reduced amounts of collagen, increased inflammation, thinning of the fibrous cap, and increased cholesterol in the necrotic core. Based on our current understanding, these processes result in plaque fissuring or rupture at the carotid bifurcation, causing either occlusive or nonocclusive thrombus formation. The dominant mechanism of stroke is believed to result from distal thromboembolism to the anterior cerebral circulation. However, a number of considerations, such as the size and composition of the embolus, the presence of contralateral disease, the anatomy of the circle of Willis, and the activity of fibrinolytic pathways, may attenuate or accentuate the clinical consequence of the pathologic event. Consequently, the same pathologic event may result in a reversible neurologic deficit (i.e., transient ischemic attack [TIA]), an irreversible neurologic deficit (i.e., stroke), or no symptoms at all.

Natural History of Carotid Artery Bifurcation Disease

In clinical practice, two dominant factors are used to determine the risk of ischemic complications from a lesion of the carotid artery bifurcation: the symptomatic status of the lesion and the severity of stenosis. Although many of these data are derived from the medical arms of the large randomized CEA trials performed between the late 1980s and early 2000s, these considerations continue to be used as the major criteria for choosing patients for endovascular procedures and for enrolling subjects in carotid endovascular trials.

Symptomatic lesions of the carotid bifurcation are associated with a high risk of recurrent ischemic stroke. In the North American Symptomatic Carotid Endarterectomy Trial (NASCET), the risk of any ipsilateral stroke at 2-year follow-up in medically treated patients with symptomatic stenoses of 70% to 99% was 26%. Among patients with symptomatic stenoses of 50% to 69%, the 5-year risk of any ipsilateral stroke was 22.2%. There is a close temporal relationship between these recurrent strokes and the index event, with a steep exponential decline in risk within the first months, followed by a more gradual decline and ultimate normalization of risk at 2 to 3 years ( Fig. 46.3 ).

By contrast, asymptomatic lesions of the carotid bifurcation are associated with a much lower risk of ischemic stroke. Over a 5-year period after an asymptomatic carotid stenosis was diagnosed (more than 60% by ultrasound), the risk of any stroke among medically treated patients in the Asymptomatic Carotid Surgery Trial (ACST) was 11%. Not surprisingly, the risk of stroke was constant over the duration of the study. The implication from these findings is that carotid revascularization should be performed as expediently as possible after a neurologic event caused by a culprit symptomatic stenosis, whereas intervention for an asymptomatic lesion may be approached in a more elective fashion.

Among symptomatic patients, a close relationship between the severity of stenosis as assessed by careful angiographic methods and subsequent risk of ipsilateral stroke has been demonstrated. The relationship is nonlinear, with a steep increase in risk associated with the tightest degree of stenosis ( Fig. 46.4 ). However, for symptomatic patients with “near-occlusion” of the ICA—defined as a stenosis causing obstruction to flow sufficient to result in a decrease in the ICA diameter beyond the lesion ( Fig. 46.5 )—there are data to suggest that the risk of recurrent stroke is reduced compared with patients with severe stenosis without features of near-occlusion. One potential explanation for this finding is the reduced likelihood of distal cerebral embolization caused by diminished flow distal to a critical stenosis. Among asymptomatic patients, the association between stenosis severity and risk of subsequent stroke has been inconsistent. This finding likely underscores the heterogeneous nature of carotid plaque histology in asymptomatic patients and suggests that assessments of plaque vulnerability may be a more potent predictor of recurrent events than severity of stenosis in this patient group.

Currently there are more sophisticated models to predict the risk of stroke in patients with carotid disease, particularly for symptomatic patients. In addition to stenosis severity, these models incorporate variables such as age, sex, nature of the presenting symptomatic event, time since the index event, plaque surface morphology, and transcranial Doppler findings to provide a more individualized estimate of risk. However, these models have yet to be incorporated into patient selection criteria in randomized trials to more fully establish their clinical relevance.

Benefit of Carotid Revascularization

The benefit of carotid revascularization in patients with carotid artery disease has been documented in several randomized controlled trials (RCTs) comparing medical therapy with surgical revascularization (i.e., CEA). These data are extremely important in any discussion of endovascular therapy for carotid bifurcation disease because they form the cornerstone justifying revascularization in certain subsets of patients. In a pooled analysis of data from the three major RCTs in symptomatic patients, CEA compared with medical therapy reduced the end point of stroke or operative death at 5 years in patients with carotid stenoses of 50% or greater, as assessed by carotid angiography using the NASCET criteria ( Fig. 46.6 ). This benefit was more pronounced in patients with stenoses of 70% to 99% (absolute risk reduction [ARR] 15.3%; 95% confidence interval [CI] 9.8% to 20.7%) than in those with stenoses of 50% to 69% (ARR 7.8%; 95% CI 3.1% to 12.5%). In addition, the crossover of the event-free curves occurred very early in the patient cohort with 70% to 99% stenoses (1 to 2 months) compared with the patient cohort with 50% to 69% stenosis (1 year). The incidence of perioperative stroke and/or death in these studies was uniformly less than 6%; the benefits derived from CEA are predicated on the maintenance of similar procedural outcomes. No significant benefit was observed in patients with near-occlusion of the carotid artery (ARR 0.1%; 95% CI −10.3 to 10.2), likely related to the lower risk of recurrent stroke with medical therapy in this group. These studies were performed in the late 1980s and early to mid-1990s; therefore the only stipulated medical therapy in the nonsurgical arm was aspirin. Contemporary medical therapy would likely attenuate the observed benefit associated with CEA. However, given the magnitude of the observed benefit associated with CEA in symptomatic patients, investigators have been reluctant to repeat randomized studies using contemporary medical therapy alone as a treatment arm.

Compared with medical therapy, CEA has also been shown to significantly reduce the incidence of stroke or operative death at 5-year follow-up in asymptomatic patients with carotid stenoses of 60% or greater, as assessed by carotid ultrasound (11.8% vs. 6.4%; ARR 5.4%; 95% CI 3% to 7.8%). It is important to emphasize that in this asymptomatic population, the early hazard associated with revascularization persists up to 2 years from the time of CEA. If the life expectancy of the patient is less than 5 years, then significant benefit should not be anticipated. In addition, participation in these trials involving patients with asymptomatic carotid stenoses required documentation of a perioperative stroke and death rate of less than 3% at the investigation site, and the generalization of these findings is predicated on reproducing similar procedural outcomes.

Percutaneous Carotid Revascularization

Initial animal experimentation with percutaneous carotid revascularization began in the late 1970s and was followed by the first clinical reports of carotid angioplasty in the early 1980s. The first rigorous clinical testing of percutaneous carotid revascularization began in the mid-1990s. Although these studies demonstrated feasibility, two subsequent pivotal developments allowed percutaneous carotid revascularization to emerge as a viable alternative to CEA in the treatment of carotid disease: the ability to provide protection from distal embolization at the time of intervention, using a variety of embolic protection devices (EPDs), and the use of self-expanding stents. Carotid artery stenting (CAS) using self-expanding stents in combination with embolic protection represents the contemporary approach to carotid revascularization.

Carotid Artery Stenting: The Procedure