Carotid stenting or surgery did not improve memory or thinking in the CREST-2 trials

Many older adults have narrowing in the carotid arteries, the large blood vessels in the neck, without ever having a stroke. Studies show that asymptomatic carotid artery stenosis is associated with diminished cognition, and some doctors hoped that opening the arteries would protect memory as well as prevent strokes.

The CREST-2 trials (the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trials) put that hope to the test. In results published in JAMA (the Journal of the American Medical Association), neither stenting nor surgery improved memory or thinking over up to four years. The same trials’ stroke results, reported last year, point in a different direction, and together they give a clearer picture of what the procedures can and cannot do.

What carotid artery stenosis is

Your carotid arteries are two large blood vessels in your neck that carry blood to the brain. In carotid artery disease they narrow, usually because of fatty plaque, and the condition is serious because it can block the blood flow to your brain, causing a stroke. It often causes no symptoms until the narrowing is severe.

Narrowing without symptoms is uncommon overall: its prevalence is low in the general population but increases with age. The US Preventive Services Task Force recommends against screening for asymptomatic carotid artery stenosis in the general adult population, because it judged the harms of screening to outweigh the benefits. Treatment options include medicines, surgery to remove the plaque, known as endarterectomy, and stenting, where a small mesh tube holds the artery open.

What CREST-2 found about strokes

The main question for the trials was whether a procedure prevents strokes better than medicines alone. The researchers ran two parallel trials across 155 centers in five countries, in patients whose artery was narrowed by 70% or more but who had no recent symptoms. Every patient received intensive treatment of blood pressure, cholesterol and other risk factors; half in each trial also had a procedure.

Stenting helped. In the stenting trial the 4-year rate of stroke or death around the procedure, or a later stroke on the treated side, was 6.0% with medicines alone and 2.8% with stenting. Surgery was less clear: in the endarterectomy trial the rates were 5.3% and 3.7%, and carotid endarterectomy did not lead to a clear benefit that could be separated from chance.

Both procedures carried an up-front cost. In the first 44 days, the stenting group had seven strokes and one death, against none with medicines alone, and the surgery group had nine strokes against three.

Did opening the carotid artery help memory?

The memory results come from the same patients. Among 2366 US study patients, 2165 (91.5%) participated in cognitive assessments. They took five tests of learning, memory, planning, attention and speed by telephone, before treatment and each year for up to four years, with testers who did not know which treatment each person had.

Neither procedure made a measurable difference. The gaps between groups were tiny, far smaller than the difference the researchers had set in advance as meaningful, and no single test showed a benefit. The authors conclude that revascularization with either stenting or endarterectomy did not measurably improve cognitive function at up to 4 years of follow-up.

What about people with reduced blood flow to the brain?

One theory held that a tight narrowing starves part of the brain of blood, and that people with the worst flow would gain most from opening the artery. Reduced blood flow to the brain in people with this narrowing is associated with reduced cognition, so a companion study, CREST-H (the hemodynamics substudy), tested that group directly.

It enrolled 392 CREST-2 participants and measured blood flow with brain perfusion scans. The key comparison was among 51 people whose thinking scores were already low at the start, 25 who had a procedure and 26 who did not. Over a year, their scores changed about the same whatever their blood flow. The authors conclude that opening the artery does not appear to improve thinking by restoring flow to the brain in chronic asymptomatic carotid stenosis. The group was small and followed for only a year.

How CREST-2 fits with other carotid trials

CREST-2 is one of three recent trials that asked whether people without symptoms still need a procedure now that medicines have improved. A meta-analysis pooled CREST-2 with two European trials, covering 3,438 patients.

Taken together, the three trials were inconclusive, partly because one European trial also included people with earlier symptoms. In the analysis restricted to purely asymptomatic populations, procedures went with fewer strokes over the long term but more complications around the time of the operation: roughly 1 stroke avoided for every 37 people treated, and 1 extra complication for every 69. The authors conclude that contemporary medical therapy remains the foundation of management, with procedures reserved for carefully selected patients.

What the carotid trials cannot tell us

Average follow-up for the memory tests was a little over two years, so the trials cannot rule out effects that take longer to appear, and testing by telephone is less detailed than a face-to-face assessment. Everyone had intensive medical treatment, which may itself protect the brain.

The results apply to people with narrowing but no symptoms, not to those who have already had a stroke or mini-stroke. The stroke benefit of stenting comes mainly from one trial, and results across the three recent trials were not consistent.

What the carotid results add up to

Taken together, the trials separate two questions. On memory and thinking, neither procedure made a difference, including in people with reduced blood flow to the brain. On strokes, stenting lowered 4-year risk while surgery showed no clear benefit, and both carried early risks.

The meta-analysis authors recommend that procedures follow individualized risk assessment and shared decision-making with a specialist. Every patient in CREST-2, with or without a procedure, was on intensive medical therapy, which the same authors describe as the foundation of management.

Sudden weakness, numbness, trouble speaking or loss of vision on one side are signs of a possible stroke or mini-stroke and need emergency care.