Whether carotid stenting has any advantage over carotid surgery (endarterectomy)—and for which patients—is still a topic of study and debate.
Treatment of carotid atherosclerosis and stenosis is important in preventing stroke and its comorbidities. Today, three main treatments exist: medical management (lipid-lowering, antihypertensive, and antiplatelet therapy), surgery, and, more recently, carotid angioplasty and stenting. The rationale for these treatments is to decrease the risk of cerebral infarction by stabilizing or removing plaque and improving blood flow.
Surgery has proven beneficial in patients with symptomatic carotid stenosis greater than 50% or asymptomatic stenosis greater than 60%, but it is risky in some patients. Stenting has evolved in part from the success of surgery and the need for alternative treatments for patients who are at unacceptable risk of perioperative complications. However, it does not have a clear advantage over surgery in patients at average risk. Further, its use in patients with asymptomatic stenosis of any severity is still controversial.
In this paper we review the major trials of carotid endarterectomy and stenting and summarize what we know today about who should undergo these therapies.
NOT ALL STROKES ARE DUE TO CAROTID ATHEROSCLEROSIS
Depending on the institution’s referral pattern and population served, between 80% and 90% of strokes are ischemic (the rest being hemorrhagic).1 Atherosclerosis of large arteries (typically defined as more than 50% stenosis of a major brain artery or branch cortical artery2) is just one cause of ischemic stroke, but it is an important one. Other identifiable causes of ischemic stroke include cardioembolism and small-artery occlusion (lacunar stroke), and some cases are idiopathic.
Large-artery atherosclerotic disease can damage the brain gradually, with carotid stenosis resulting in hypoperfusion and subsequent cerebral infarction. More commonly, however, the carotid plaque often seen in large-artery atherosclerotic disease can ulcerate and occlude the vessel acutely or generate platelet aggregates that may embolize, resulting in cerebral infarction or transient ischemic attack.
In the Lausanne Stroke Registry,3 the rate of ischemic stroke in patients with a greater than 50% large-artery stenosis ranged from 27% in 1979 to 17% in 2003, the decline likely being due to therapeutic advances.
SURGERY BEATS MEDICAL THERAPY FOR CAROTID ATHEROSCLEROSIS
Four landmark trials provided substantial evidence that carotid endarterectomy is better than medical management in patients with symptomatic or asymptomatic high-grade stenosis. These trials indirectly paved the way for carotid stenting.
The North American Symptomatic Carotid Endarterectomy Trial (NASCET)
Patients at 50 clinical centers who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke were randomized to undergo surgery (carotid endarterectomy) or no surgery. All patients received maximal medical management consisting of blood pressure control, lipid management if indicated, and antiplatelet therapy with aspirin. At baseline, 37% of patients were taking 650 mg or more of aspirin per day, and 11% were taking less than 325 mg per day. The patients were stratified into two prespecified groups on the basis of the severity of carotid stenosis: those with narrowing of 30% to 69% and those with narrowing of 70% to 99%.
Results in high-grade stenosis. In August 1991, the investigators published their results in patients with symptomatic high-grade (70%–99%) stenosis.4 Surgical treatment was more beneficial than medical management alone: the cumulative risk of any ipsilateral stroke at 2 years was 26% in the medical group and 9% in the surgical group, an absolute risk reduction of 17%. The benefit of endarterectomy was still apparent at 8 years of follow-up.5
Results in moderate stenosis. In 1998, the investigators published their results in patients with symptomatic moderate (< 70%) stenosis.5 Surgery was more beneficial than medical therapy in this subgroup as well: at 5 years, the rate of any ipsilateral stroke in patients with 50% to 69% stenosis was 15.7% in those treated surgically and 22.2% in those treated medically (P = .045). In patients with less than 50% stenosis, the 5-year stroke rate was not significantly lower with endarterectomy than with medical therapy.
The European Carotid Surgery Trial (ECST)
The ECST,6 published in 1998, corroborated the NASCET findings. This multicenter, randomized, controlled trial enrolled 3,024 patients with symptoms of at least one transient ischemic attack in the distribution of one or both carotid arteries.
Results. In patients with stenosis of greater than 80% (60% by the NASCET criteria for calculating angiographic stenosis), the frequency of major stroke or death at 3 years was 26.5% in the control group and 14.9% in the surgery group, an absolute difference of 11.6%.
The Endarterectomy for Asymptomatic Carotid Artery Stenosis (ACAS) trial
The NASCET and ECST studies made it clear that select groups of patients with symptomatic carotid stenosis benefit from carotid endarterectomy. But what about patients with stenosis but no prior stroke?
The ACAS trial aimed to find out.7 In this pivotal study, 1,662 patients with asymptomatic carotid artery stenosis greater than 60% were randomized to receive either medical therapy alone or medical plus surgical therapy.
Results were published in 2004. After a median follow-up of 2.7 years, the aggregate 5-year risk of ipsilateral stroke, any perioperative stroke, or death was estimated to be 5.1% in the surgical group and 11.0% in the medical group, a relative risk reduction of 53%. However, for surgery to be beneficial, the rate of perioperative death and other serious complications had to be less than 3%, and the expected patient survival had to be at least 5 years.
Of note, the benefit of carotid endarterectomy in this study was predominantly in men, with less of a benefit for women and diabetic patients. Furthermore, even though endarterectomy was beneficial in this asymptomatic cohort, the overall benefit in terms of stroke risk reduction was small compared with that in NASCET and ECST, in which patients had symptomatic disease.
The Asymptomatic Carotid Surgery Trial (ACST)
In this European version of ACAS, published in 2004, 3,120 patients with asymptomatic carotid narrowing on ultrasonography were randomized to undergo surgery or medical therapy.
Results. The risk of stroke or death within 30 days of carotid endarterectomy was 3.1%. In patients younger than 75 years who had carotid narrowing of 70% or more, immediate surgery decreased the net 5-year stroke risk from 12% to 6%.8