All you need to know about carotid artery disease
Large vessel disease encompasses an extremely wide range of extracranial and intracranial cerebrovascular disorders. In this episode, we focus on atherosclerotic disease of the carotid system, which is the most common form of large vessel disease-associated infarction. Dr. Ali Hamedani conducts this interview with me as we navigate through the mechanisms of infarction in large artery atherosclerosis and how these patients are managed.
Diagnosis. Often, large vessel atherosclerotic disease is identified as a part of the routine workup for stroke. Occasionally, asymptomatic large vessel athero is recognized incidentally during carotid auscultation by an eager internist or cardiologist (a rule of thumb here is 75% of all extracranial carotid plaques with 75% stenosis can be identified using a stethoscope). However, many other instances of asymptomatic stenosis are identified as part of medical clearance for other vascular interventions and major surgeries, and then the neurologist is asked to weigh in on the perioperative risks of stroke and whether carotid revascularization is indicated before or after the planned surgery.
Pathophysiology. As in many other vascular diseases, common risk factors for the development of large artery atherosclerosis include hypertension, tobacco use, and diabetes. Male gender also increases the risk of progression, as does radiation for head and neck cancers. Temporally speaking, carotid atherosclerosis develops over decades (see figure), and while genetics plays a large role, there are no congenital atherosclerotic lesions.
So we are left with the question of, “when should physicians intervene?” In a pooled analysis of two international trials trials, there was a 4.6% absolute reduction in 5-year ipsilesional stroke in patients with revascularization for 50-69% stenosis by NASCET criteria, and a more impressive 16% 5-year risk reduction in patients with severe stenosis (70-99%). After pooling data from 3 major trials, the NNT to prevent an ipsilateral stroke or peri-operative death is 22 for a 50-69% stenosis, but drops to 6.3 for 70-99%, and for a near occlusive lesion, there is no overt benefit in the short or long-term, and there is even a trend to medical therapy being more optimal than surgery in that instance. Therefore, many vascular surgeons recommend intervention for symptomatic carotid atherosclerotic disease for patients with 50-99% stenosis. And that’s just a general rule to follow, but other factors like location of the lesion, gender of the patient, and surgical candidacy are also powerful predictors of success with revascularization. For more info on these nuances, I will refer you to the podcast.
If untreated with revascularization, there is an estimated 25% 5-yr risk of ipsilesional stroke according to pooled analyses of the medical arms of several major trials assessing patients with symptomatic carotid atherosclerosis. Compared to every other major etiology of stroke, large vessel disease remains the most common mechanism, and large artery atherosclerosis carries the greatest risk for recurrence if improperly managed.
Stent vs. CEA. In perhaps the most important trial to date which addressed this question, the CREST investigators randomized 2500 patients to stenting or endarterectomy, and about 47% of patients had asymptomatic large vessel disease. The primary endpoint of any stroke, MI, or death in the peri-operative period, or ipsilesional stroke within 4 years was the same, regardless of whether the patient underwent stent or CEA. That being said, there was a slightly lower risk of perioperative stroke in the CEA group, and a slightly lower risk of MI in the stenting group. Older patients in general fared better with CEA than with stenting, and young patients fared better with stenting than with CEA. And while we think of these results when deciding which patient should go to the OR and who should go to the angio suite, we also consider are location of the plaque (if its too high up or surgically inaccessible, but still extracranial, then stenting is really the only option; but if there is dense atherosclerotic disease of the aortic arch and carotid which might risk peri-operative stroke too greatly if stenting is considered, that patient might go for CEA). And we also consider the morphology of the plaque (with more angry, heterogeneous plaques with intraplaque hemorrhage among those we might prefer to send to the OR for endarterectomy).
Asymptomatic carotid disease is an interesting twist in the plot here. Compared to the 25% 5-yr risk of ipsilesional stroke in a previously symptomatic carotid lesion, data from ACAS, ACST, and ACSRS showed a 5-10% 5-yr risk of ipsilesional stroke in incidentally identified carotid plaque. So it’s a lower, but not insignificant risk. And whether to intervene on these patients is still controversial, and at least one ongoing trial to my knowledge, the CREST-2 trial, is evaluating the risks/benefits of intervention for high-grade asymptomatic large vessel disease. Current data (and a Cochrane review) suggests that patients with asymptomatic stenosis of 60-99% by NASCET criteria would benefit from revascularization. 30-day perioperative stroke risk was about 3%, with an impressive 30% reduction in 3-yr stroke events among patients in the intervention arm. The combined endpoint of death or stroke was also reduced by about 30% if endarterectomy was performed. These results should be interpreted with caution because, like I mention in the podcast, the 5-yr risk of ipsilesional stroke in an asymptomatic carotid is low (5-10%), meaning there’s only about a 1% annual absolute risk reduction with surgery for asymptomatic atherosclerotic disease. This is the same kind of annual risk reduction we see in run-of-the-mill stroke patients who are treated with aspirin versus those who are not.
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