Carotid endarterectomy (CEA) has long been the standard treatment for symptomatic or hemodynamically significant carotid artery stenosis. The introduction of carotid artery stenting (CAS) has provided another, sometimes controversial, option in the treatment of carotid artery disease. The debate is the result of the design of prior studies, lack of good controlled data, and issues of low operator stenting experience, all of which may have contributed to the potential for complications and error.
The results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) were published in the New England Journal of Medicine on July 1, 2010. This multicenter trial enrolled 2,502 patients at 108 centers in the United States and 9 in Canada.
Centers were required to have a multidisciplinary team consisting of a neurologist, an interventionist, a surgeon, and a research coordinator. Selection criteria were carefully documented and were in strict compliance. The interventionists were certified on the basis of their carotid stenting results, participation in hands-on training, and participation in a lead-in phase of training. The surgeons also had to document their experience.
"These requirements satisfied some of the concerns and issues related to uneven operator experience in the prior 2 trials," according to David R. Holmes, M.D., an interventional cardiologist at Mayo Clinic.
This large trial included both symptomatic (53%) and asymptomatic (47%) patients with carotid artery stenosis. The eligibility criteria used were:
Criteria were expanded during the course of the study to include asymptomatic patients.
Patient exclusion criteria included prior stroke severe enough to confound the assessment of study end points or another potential cause for stroke, such as atrial fibrillation or the presence of unstable angina.
Of note, the patients could be randomized on the basis of ultrasonography criteria. This stipulation had important implications; some patients who were randomly assigned to carotid stenting at the time of intervention were subsequently found to have anatomic characteristics that made them not suitable for carotid stenting, such as the lack of a distal landing zone for the embolic protection device. Using intention-to-treat methods, however, data from these patients were carried forward as though they continued to be enrolled in the stenting arm of the study.
Patients were randomly assigned to either conventional endarterectomy or carotid stenting with a relatively early-generation stent and a distal embolic protection filter. The primary end point was a composite of any stroke, myocardial infarction, or death during the periprocedural period or an ipsilateral stroke within 4 years of randomization. There was no significant difference in this primary end point between CAS and CEA (7.2% vs 6.8%; P=.51).
During the periprocedural period, the incidence of the primary end point was also similar; however, there were differences in specific individual end points. While there was no difference in death (0.7% with CAS, 0.3% with CEA), stroke, which was typically minor, occurred more frequently in CAS (4.1% vs 2.3% in CEA; P=.01), while myocardial infarction occurred more frequently in CEA (2.3% vs 1.1% in CAS; P=.03).
There was a marked imbalance in cranial nerve palsy, which occurred in 4.7% of CEA patients vs 0.3% of CAS patients. After the periprocedural period, ipsilateral stroke was similarly low in both treatment arms (2.1% with CAS and 2.4% with CEA).
The 4-year rate of stroke or death in the CAS group was 6.4% vs 4.7% in the CEA group. In patients who were symptomatic, the respective rates were 8.0% vs 6.4% (P=.14); in asymptomatic patients, those rates were 4.5% vs 2.7% (P=.07).
The CREST results document that CAS and CEA in experienced hands are associated with similar rates of primary composite outcome. Procedural stroke, myocardial infarction, or death and subsequent ipsilateral stroke among patients with either symptomatic or asymptomatic carotid stenosis were not significantly different between patients treated with stenting and those treated with endarterectomy.
There was a difference in the individual end points, with more CAS patients having stroke, which was typically minor, while more CEA patients had myocardial infarction and cranial nerve palsy.
Accordingly, the authors concluded that carotid revascularization performed by highly qualified surgeons and interventionists is effective and safe and that the low absolute risk of recurrent stroke suggests that both CAS and CEA are clinically durable.
"Subsequently, there have been other important developments to be considered. The concern about periprocedural embolism has been addressed using new proximal protection devices, which have drastically reduced the incidence of embolic strokes associated with stenting," says Dr. Holmes. "The trial results indicate that the therapeutic choice should be individualized on the basis of anatomic considerations, comorbid conditions, and patient choice."