Ischemic stroke remains an important cause of mortality in the United States. In 2022 there were approximately 165,000 deaths due to stroke which was the second leading cause of cardiovascular disease death.1 Each year approximately 795,000 people in the United States have a stroke.2 Based on the TOAST classification of stroke etiologies, large artery atherosclerosis (LAA) is defined as >50% stenosis of an extra or intracranial artery secondary to atherosclerotic disease which is thought to be causally related to the stroke. Approximately 13% of ischemic strokes annually are thought to be secondary to LAA.2

Atherosclerotic disease is due, in part, to a chronic inflammatory process that causes plaque formation in the arterial wall. Areas of bifurcation are particularly susceptible to plaque formation due to turbulent blood flow. Plaque formation starts with endothelial cell dysfunction which leads to accumulation of lipoproteins that triggers an inflammatory response. Monocytes are recruited and ingest lipoproteins leading to formation of foam cells and a fatty streak. Smooth muscle proliferation and extracellular matrix deposition of lipids causes formation of a lipid-rich necrotic core. A fibrous cap is developed to stabilize this necrotic core causing plaque formation on the vessel wall. Until the fibrous cap matures, the lipid rich core is at high risk for rupture. If the plaque ruptures, the sub endothelium is exposed to blood triggering the coagulation cascade and formation of a thrombus.3 As the fibrous cap matures, the plaque becomes calcified and less likely to rupture.

Operative or interventional management (i.e., endarterectomy, angioplasty/stenting or trans carotid artery revascularization) of symptomatic carotid disease has traditionally involved correcting the area of arterial narrowing guided by stenosis severity combined with medical therapy. Symptomatic carotid disease is defined as carotid stenosis that is related to ischemic stroke, transient ischemic attack, or amaurosis fugax, when the symptomatic event has occurred in the preceding six months. The degree of carotid stenosis can be measured using several classification systems such as the NASCET criteria or ECST method using CTA imaging. Ultrasonography can also be used to estimate stenosis based on vessel flow velocities. Clinical trials showed benefit for revascularization therapy for high grade stenosis (70-99%).

The 2021 AHA Secondary Stroke Prevention Guidelines recommend revascularization via carotid endarterectomy (CEA) based on the VA309, ECST, and NASCET trials which all showed benefit for treating high grade extracranial carotid stenosis (70-99%).2 A summary of the key findings of these trials and their timeline of publication can be found in table 1. The benefit for revascularization for moderate stenosis (50-69%) is based on additional patient factors such as comorbidities, age, sex, and perioperative mortality risk.4 There was no benefit of revascularization for those with <50% stenosis. NASCET, ECST, and VA 309 were conducted over 30 years ago, and before the advent of current medical therapies. Newer trials, such as CASCOM and ECST2, suggest that modern intensive medical therapy may be as effective as surgical revascularization for secondary stroke prevention and mortality benefit in select patients with symptomatic carotid disease, but these studies enrolled a relatively low number of patients. The preliminary 2-year ESCT2 data did not find a difference in medical versus surgical management of low and moderate risk symptomatic carotid artery disease for MACE outcomes, although the final results are still pending.5 These findings suggest that for the appropriate patient, medical management of symptomatic carotid artery disease may be a reasonable alternative to surgery.