ACCEL | Carotid atherosclerosis accounts for ~10% of ischemic stroke cases. Multifaceted medical therapy reduces the risk of stroke in patients with carotid stenosis and new guidelines make it the baseline therapy for everyone with extracranial carotid stenosis.^1,2 That means whether the stenosis is mild (< 50%), moderate (50% to 69%), or severe (> 70%), therapy should include risk factor control, antiplatelets, statins, and ACE inhibitors.

Want something more specific than that? In the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis),³ patients with transient ischemic attack or stroke in the past 30 days and 70% to 99% stenosis of a major intracranial vessel, such as the middle cerebral artery or basilar artery, were enrolled. All patients received aggressive medical therapy:

• Aspirin + clopidogrel for the initial 90 days
• Aspirin alone beyond 90 days
• Rosuvastatin to a target low-density lipoprotein level <70 mg/dL
• Systolic blood pressure-lowering target
• <140 mm Hg for nondiabetic patients
• <130 mm Hg for diabetic patients

Aggressive therapy also included the Nationwide Better Health – INTERVENT program, which is a commercial, evidence-based, lifestyle management, and chronic disease risk reduction service targeting key factors such as smoking cessation, exercise, and diet.

The approach worked: the primary endpoint occurred in 12.2% of patients at 1 year, or approximately 50% less than the projected event rate. (The primary endpoint was: stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period; or stroke in the territory of the qualifying artery beyond 30 days.) This was superior to the more invasive approach with optimal medical therapy (OMT) plus intracranial stenting at 1 year (20.0%; p = 0.009), which illustrates the potential of aggressive medical therapy. So should revascularization fall to the wayside now in favor of OMT? Well, ask interventionalists and there is still plenty of support for appropriate revascularization and stenting; ask everyone else and there is typically a lot of support for OMT. However, the literature is—shall we say—more nuanced than that.

Revascularization

Revascularization with carotid endarterectomy (CEA) or carotid artery stenting (CAS) can benefit select patients, with several characteristics that may influence the choice of revascularization technique (Table). New guidelines note, for example, that it’s reasonable to consider patient age in choosing between CAS and CEA. For individuals older than 70, the U.S. guidelines state that CEA may be associated with better outcomes compared with CAS, but for younger patients, CAS is equivalent to CEA.¹

Risk assessment helps guide therapy, and whether or not the patient is symptomatic plays an outsized role in such assessment. In a recent review article for the Journal of the American College of Cardiology,⁴ Seemant Chaturvedi, MD, and Ralph L. Sacco, MD, noted that individuals with an asymptomatic internal carotid artery (ICA) stenosis of 60% to 99% have an annual risk of stroke—based on 1990s medical therapy—of 2% to 2.5% per year. On the other hand, symptomatic carotid stenosis >70% carries an annual stroke risk of 10% to 15%, based on 1990s medical therapy.

One consideration when making treatment decisions for asymptomatic carotid stenosis: in a combined analysis of two trials, men had a 51% relative risk reduction in the rate of stroke with surgery, whereas women did not have a reduction in stroke after CEA.⁵ In plaque analysis studies, it has been noted that women have lower macrophage staining in carotid plaques and more smooth muscle, which provides for an overall “more stable” plaque than seen in men. Because women have been underrepresented in previous carotid stenosis trials, it may be time for a clinical trial dedicated to women with carotid stenosis.

What are the characteristics of vulnerable carotid plaque? This was evaluated recently⁶ and 5-year stroke risk was associated with:

• plaque thrombus
• fibrous content
• macrophage infiltration
• high microvessel density
• overall plaque instability

However, vulnerable carotid plaque was not associated with cap thickness, calcification, intraplaque hemorrhage, or lymphocyte infiltration.

Where does that leave us? According to Dr. Sacco, here are a few points to keep in mind:

• CEA is of proven value for symptomatic carotid stenosis >50% and CAS is an alternative, especially in patients under the age of 70. In symptomatic patients older than 70, endarterectomy seems to be associated with better outcomes. Choice of intervention depends on age, degree of stenosis, and other comorbidities.
• Risks for CEA and CAS have declined, but the optimal treatment for asymptomatic stenosis is unclear.
• Stroke risk predictors for asymptomatic patients with carotid stenosis include plaque echolucency, thrombus, and CMR subclinical markers.
• Medical therapy has improved for ICA stenosis and includes antiplatelets, statins, and aggressive risk factor modification.

Take-Aways

• Carotid endarterectomy (CEA) is of proven value for symptomatic carotid stenosis > 50%, and carotid artery stenting (CAS) is an alternative, with choice of intervention depending on age, degree of stenosis, and other comorbidities.
• Risks for CEA and CAS have declined, but the optimal treatment for asymptomatic stenosis is unclear, although stroke risk predictors (such as sex, given that males benefit much more from surgery) should be taken into account when selecting therapy.
• Medical therapy has improved for inter-nal carotid artery stenosis and includes antiplatelets, statins, and aggressive risk factor modification.

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References

1. Kernan WN, Ovbiagele B, Black HR, et al. Stroke. 2014;45:2160-236.
2. Meschia JF, Bushnell C, Boden-Albala B, et al. Stroke. 2014;45:3754-832.
3. Chimowitz MI, Lynn MJ, Derdeyn CP, et al., for the SAMMPRIS Trial Investigators. N Engl J Med. 2011;365:993-1003. (Correction in N Engl J Med. 2012;367:93).
4. Chaturvedi S, Sacco RL. J Am Coll Cardiol. 2015;65:1134-43.
5. Rothwell PM, Goldstein LB. Stroke. 2004;35:2425-7.
6. Howard DP, van Lammeren GW, Rothwell PM, et al. Stroke. 2015;46:182-9.

Keywords: CardioSource WorldNews Interventions, Carotid Artery Diseases, Atherosclerosis, Risk Assessment, Stroke

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