By Annette M. Boyle

Salomeh Keyhani, MD, MPH

Salomeh Keyhani, MD, MPH

SAN FRANCISCO — For selected patients with carotid stenosis, national guidelines recommend revascularization for primary or secondary prevention of stroke. Increasingly, though, it appears that veterans who could benefit the most from these procedures do not have them, while those who might receive marginal benefit may have them too often.

In the U.S., stroke is a leading cause of disability and the fourth-leading cause of death. While atherosclerosis of the internal carotid arteries causes 10%-15% of ischemic strokes, many patients have carotid stenosis of 50% or more without experiencing a stroke. For treatment purposes, guidelines consider patients who have had an ischemic stroke or transient cerebral ischemic symptoms within the past six months to be symptomatic and those who have not had a stroke or transient ischemic attack (TIA) to have asymptomatic carotid stenosis.


Adjusted Odds Ratio of NOT Receiving Carotid Intervention Among Eligible Patients with Severe Symptomatic Carotid Stenosis

The American Heart Association and American Stroke Association (AHA/ASA) recommend carotid endarterectomy (CEA) within six months of a nondisabling ischemic stroke or TIA for patients who have more than 70% stenosis, based on noninvasive imaging, or more than 50% stenosis as indicated by catheter angiography, and a less than 6% risk of perioperative stroke or death. Carotid stenting (CAS) could also be considered for these patients.

The American Academy of Neurology guidelines say CEA also may be considered for patients with 50-69% symptomatic stenosis, if they have a life expectancy of more than five years and a risk of perioperative stroke or death of less than 6%.

Surgical revascularization dramatically improves survival rates in symptomatic patients, with patients who have had CEA achieving five-year stroke-free survival rates of 93% compared to 75% for all patients with carotid stenosis.

Limited Benefit for Asymptomatic Patients

CEA may also be considered in asymptomatic patients with more than 70% stenosis, when the perioperative risk of stroke or death is low and the expected life expectancy exceeds five years, according to the AHA/ASA guidelines.

While “it is recommended for selected patients, the evidence base is evolving, and current ongoing studies, including a randomized clinical trial funded by the National Institutes of Health (CREST II), will shed light on this issue,” said Salomeh Keyhani, MD, MPH, a physician at the San Francisco VAMC and an associate professor of medicine at the University of California, San Francisco.

Keyhani presented results of a study of carotid revascularization in asymptomatic veterans with carotid stenosis at the AcademyHealth Annual Research Meeting in June, which raised serious questions about patient selection for carotid revascularization in practice.1

The study reviewed the records of 2,359 veterans who received either CEA or CAS from 2005 to 2009. Patients were considered to meet the most recent inclusion criteria, as established in the Stenting vs. Endarterectomy for the treatment of Carotid Artery Stenosis (CREST) trial, if they had more than 70% stenosis by ultrasound or 60% by angiography and did not have atrial fibrillation, severe chronic heart failure, chronic obstructive pulmonary disease or malignancy and were not on dialysis or receiving palliative care.

The researchers found that 73.3% of patients met the CREST criteria, but the overall five-year survival rate was only 69.5% — 74.4% for those who met the criteria and 55.6% for those who did not. They concluded that “even among a population who largely met trial inclusion criteria, overall survival at five years limited the potential benefit of intervention,” demonstrating the challenge of translating benefits seen in research studies into practice.

Underused for Symptomatic Patients

On the flip side, previous research by Keyhani and other VA researchers found few veterans with symptomatic carotid stenosis received carotid intervention, even though the benefits are substantial.

In a study that examined the records of 200 ischemic stroke patients admitted to a VA medical center in 2007 with at least 50% stenosis of the carotid artery, only 17% (34) received a revascularization intervention. Of the 84 veterans with stenosis of 70% or greater, 26 (31%) received intervention. Eight (6.9%) of the 116 patients with carotid stenosis of 50%-69% also received CEA.2

As several trials have shown greater benefit from revascularization in patients with severe (more than 70%) stenosis compared to those with less stenosis and the recommendations for intervention are stronger for this population, the researchers were not surprised to find intervention more common in this group.

The researchers noted that black veterans were significantly less likely to receive revascularization and less likely to have carotid imaging tests following a stroke, although they found that “this difference was largely dependent on overall low rates of post-stroke carotid imaging in both blacks and whites in just a few hospitals.”

Despite the greater benefit of CEA and CAS for symptomatic patients, with a number needed to treat of 12 vs. 100, 60% of revascularization procedures in the VA are performed on asymptomatic patients, noted Keyhani and colleagues. “Why so few patients with symptomatic disease and especially stroke receive intervention despite its superior efficacy in this population is of particular concern,” study authors pointed out.

The study did not address why more veterans with severe carotid stenosis did not receive CEA or CAS, but Keyhani told U.S. Medicine “it may be because patients are not referred for intervention in time to benefit. It may also be partly explained by whether a patient is a good surgical candidate or not.”

In the study, physicians documented that three eligible patients refused intervention and that 28 others had reasons for not wanting the procedure.

For all the unknowns, the research clearly supports two conclusions, Keyhani said. “There is clear evidence of benefit for timely carotid revascularization for patients with symptomatic carotid disease and that there is an observed quality gap in care that we need to address.”

1 Keyhani, S., Cheng E, Madden E, Halm E, Hebert P, Johanning J, Eilkhani E, Bravata D. Translating Clinical Trial Evidence into Practice—the Case of Carotid Revascularization. AcademyHealth Annual Research Meeting. June 15, 2015.

2Keyhani S, Cheng E, Ofner S, Williams L, Bravata D. The Underuse of Carotid Interventions in Veterans with Symptomatic Carotid Stenosis. Am J Manag Care. 2014;20(7):e250-e256.