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In patients with asymptomatic carotid stenosis, using ultrasound to detect the presence of microemboli or 3 or more ulcers identifies the 10% of those at high risk of stroke or death who would most benefit from revascularization, according to research published in the August 23, 2011, issue of Neurology. Until results of endarterectomy and carotid artery stenting improve, the other 90% of patients will fare better with intensive medical therapy alone, the authors suggest.

J. David Spence, MD, of the Stroke Prevention and Atherosclerosis Research Centre (London, Canada) and colleagues used transcranial Doppler to detect microemboli and 3-D ultrasound to identify ulcers in both internal carotid arteries of 253 patients with asymptomatic carotid stenosis (at least 60%). The investigators followed the patients for 3 years to determine the degree to which the presence of ulceration and/or embolization predicted stroke and mortality.

Patients’ mean age was 69.66 years. All patients were counseled on a healthy lifestyle and prescribed intensive medical therapy. Of the cohort, 4% had 3 or more ulcers and 6% had microemboli.

The presence of 3 or more ulcers predicted an increased 3-year risk of stroke (18.2% vs. 1.7%; P = 0.02) as well as death or stroke (18.2% vs. 2.1%; P = 0.03) compared with less than 3 ulcers. The stroke risk existed regardless of the side on which the ulcers were found. Moreover, 3 or more ulcers predicted stroke or death risk to a similar degree as microemboli (20% vs. 2%; P = 0.003), while 2 or more ulcers carried about half the risk of microemboli. The annual rate of ipsilateral stroke was 0.8%.

In regression analysis, risk of stroke, death, or TIA was strongly associated with microemboli (P < 0.0001) and weakly associated with ulceration (P = 0.055). On the other hand, age, sex, and severity of stenosis did not predict these events (P = 0.42, 0.68, and 0.91, respectively).

Overuse of Revascularization

“All over the United States there are interventionalists, including cardiologists, throwing stents into people who don’t need them and would be better off without them,” said Dr. Spence in a telephone interview with TCTMD. “Ninety to 95% of stenting of [asymptomatic carotid stenosis] is based on outdated clinical trial data that have been superseded by research showing that medical therapy is better.”

Notably, earlier research by Dr. Spence and colleagues showed that the 1-year risk of stroke in patients with asymptomatic carotid stenosis was 15.6% if they had microemboli detected with transcranial Doppler ultrasound but only 1% if they did not. This finding was validated by the Asymptomatic Carotid Emboli Study (ACES). In addition, a meta-analysis by Abbott et al revealed that the risk of stroke or death in asymptomatic patients has diminished with the advent of intensive medical therapy, falling below the risk associated with surgery. In a 2010 study by Dr. Spence and colleagues, stroke risk in asymptomatic patients receiving intensive medical therapy was less than 5%.

The current study shows that it is possible to identify those patients most likely to benefit from revascularization. “The presence of 3 or more ulcers in the carotid arteries on 3-D ultrasound had a risk that was equivalent to the risk of microemboli,” he said. “In this group, the 3-year risk of stroke or death was 20% with either microemboli or ulcers, and it was less than 2% with neither. [The latter is] below the risk of surgery if there are no ulcers or emboli and higher than the risk of surgery if there are either ulcers or emboli.”

Stenosis Severity Matters

William A. Gray, MD, of Columbia University Medical Center (New York, NY), said that while the research highlights the important relationship between properties of carotid plaque and the risk of stroke in asymptomatic carotid stenosis, the trial protocol leaves some important questions unanswered.

“They included patients who had carotid stenosis of 60% or more, but typically we don’t treat those patients,” he told TCTMD in a telephone interview. “We treat patients with more like 70% or 80% stenosis. It would be nice if they had stratified [outcomes] by stenosis severity, to see if it is as great or greater a predictor of outcomes.

“For patients with higher-grade stenoses [80% or more], I would submit there are no data that suggest that waiting in those patients is better than operating or stenting,” Dr. Gray asserted. “The only randomized data we have today are from the ACAS [Asymptomatic Carotid Atherosclerosis Study] and ACST [Asymptomatic Carotid Surgery Trial] trials. Those studies show the same benefit of surgery over no surgery. At about 5 years there is a 6% or 7% benefit for the patient who gets surgery.”

Moreover, the ACST trial showed that deferring surgery until a stroke or TIA has adverse consequences, he observed. Half the patients who had an event had a disabling stroke, and if those who had a TIA or stroke were then revascularized, the risk associated with the procedure doubled. “So waiting wasn’t a benign thing,” he concluded.

Dr. Gray also noted that what constitutes optimal medical care for patients with asymptomatic carotid disease is unclear. And regardless, such therapy remains underprescribed, and patient compliance is notoriously low.

Finally, he pointed out, “in the latest clinical trial, the risk of stroke or death following surgery in patients with asymptomatic carotid stenosis was 1.4%, and with stenting it was about 2%. It’s going to be hard for medical therapy to beat those numbers.”

Hope for Overcoming Polarization?

“This is a polarized argument,” observed Christopher J. White, MD, president of the Society for Cardiac Angiography and Interventions in a telephone interview with TCTMD. “There are those who believe that almost no patient with [asymptomatic carotid stenosis] needs either surgery or stenting. [But] more than 50% of all the carotid revascularization is happening in asymptomatic patients. The problem is that nobody, including the NIH, is willing to fund a trial that compares medical therapy to surgery again, [as] was done in the 90s.

“But now this paper now comes along and says, ‘We can tell you which of the asymptomatic patients are likely to have problems. Those are the people who need to have revascularization.’ he continued. “[Although] this research needs to be duplicated, it is the kind of pilot study that [stimulates clinicians to try to] reduce the number of people who get surgery unnecessarily but still [offer] surgery to the people who need it without them having a stroke.”

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