Carotid-artery stenting has emerged as a therapeutic alternative to endarterectomy for the treatment of severe cervical carotid-artery stenosis. Rosenfield et al. conducted the Asymptomatic Carotid Trial (ACT) I trial, whose primary aim was to compare the outcomes of carotid endarterectomy versus stenting with embolic protection in patients with asymptomatic severe carotid-artery stenosis who were at standard risk for surgical complications.
In this trial involving asymptomatic patients with severe carotid stenosis, stenting was noninferior to endarterectomy with regard to the primary composite end point of death, stroke, or myocardial infarction within 30 days or ipsilateral stroke within 1 year after the procedure. A new Original Article summarizes.
Clinical Pearl
• What is the basis for the current approach to revascularization in patients with asymptomatic carotid artery stenosis?
The Asymptomatic Carotid Atherosclerosis Stenosis (ACAS) and Asymptomatic Carotid Surgery (ACST) trials showed that among asymptomatic patients with carotid-artery stenosis of greater than 60% of the diameter of the artery, the risk of stroke or death was lower when immediate carotid endarterectomy was performed than when surgery was deferred. In spite of these data, revascularization for asymptomatic carotid stenosis remains controversial; current medical therapy that combines statins, antiplatelet agents, and antihypertension control has independently led to a reduction in the incidence of stroke, although reductions among patients with established severe carotid stenosis have not been shown in prospective studies.
Clinical Pearl
• Are most carotid revascularization procedures in the United States performed for symptomatic or asymptomatic atherosclerotic disease?
Most carotid revascularization procedures in the United States are carotid endarterectomies performed for the treatment of asymptomatic atherosclerotic disease. Revascularization is also performed by means of stenting with devices to capture and remove emboli (“embolic protection” devices). In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), no significant difference was found between carotid endarterectomy and stenting with embolic protection for the treatment of atherosclerotic carotid bifurcation stenosis with regard to the composite end point of stroke, death, or myocardial infarction. CREST included both symptomatic and asymptomatic patients, and it was not sufficiently powered to discern whether the carotid endarterectomy and stenting with embolic protection were equivalent according to symptomatic status.
Morning Report Questions
Q: How does carotid-artery stenting compare to carotid endarterectomy in asymptomatic patients with severe carotid artery stenosis?
A: In the study by Rosenfield et al., the primary composite end point of death, stroke, or myocardial infarction by 30 days after the procedure or ipsilateral stroke within 1 year was tested at a noninferiority margin of 3 percentage points. At 1 year, the event rate (±SE) estimated by the Kaplan–Meier method for the primary end point was 3.8±0.59% (1089 patients) in the stenting group and 3.4±0.98% (364 patients) in the endarterectomy group, with a between-group difference of 0.4 percentage points. The upper limit of the one-sided 95% confidence interval for the difference was 2.27 percentage points (P=0.01 for noninferiority), which is below the prespecified 3-percentage-point noninferiority margin for the primary end point, leading to the conclusion that stenting was noninferior to endarterectomy. The rates of stroke and survival after the procedure did not differ significantly between the two study groups over a period of 5 years.
Figure 2. Kaplan–Meier Analysis of Freedom from the Primary Composite End Point.
Figure 3. Clinical Outcomes at 5 Years after the Procedure.
Q: Describe a limitation of the ACT I trial.
A: A limitation of the ACT I trial, which was designed and began enrollment a decade ago, is the lack of a treatment group that received contemporary medical therapy only. Current multispecialty guidelines and the existing evidence support the use of carotid revascularization for treatment in selected patients. However, advances in medical treatment have resulted in a reduction in stroke risk in selected populations with neurologic symptoms. Observational studies have shown that the annual risk of a stroke among asymptomatic patients is probably less than 1% per year with modern medical therapy. Although ACT I does not address a comparison between revascularization and contemporary medical therapy alone, the declining rate of stroke and resultant variation in clinical practice has led to important new randomized trials, such as CREST 2 (ClinicalTrials.gov number, NCT02089217), that will reassess the relative benefit.