For more than 50 years, endarterectomy has been the standard alternative to medical therapy for patients with extracranial carotid stenosis who are in need of revascularization. Carotid stenting, a minimally invasive treatment that was begun less than 20 years ago, has less of a proven track record, in part because it is a newer procedure.
The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), led by Thomas G. Brott, M.D., a neurologist at Mayo Clinic in Florida, was a randomized treatment trial designed to compare the outcomes associated with both procedures. With 2,502 patients from 117 participating institutions in the United States and Canada, it is the largest such study ever conducted.
The results of CREST showed that both procedures were associated with similar rates of the outcome measure (New England Journal of Medicine. 2010;363:11-32). Configured as a primary composite end point, the outcome measure was ipsilateral stroke, myocardial infarction (MI) or death.
Neurological and cardiac functions were assessed at the periprocedural period (within hours after the procedure and one month later) and at six-month intervals for the four-year duration of the study.
Study participants were men and women who had been predetermined by vascular experts to need a revascularization procedure. Half were asymptomatic and half were symptomatic. (Symptomatic was defined as having evidence of a transient ischemic attack, amaurosis fugax or minor nondisabling stroke involving the carotid artery within 180 days of entering the study.) Eligible patients were randomly assigned to undergo either endarterectomy or stenting.
Overall, in the perioperative period, the rates of stroke, MI and death were low:
The combined stroke and mortality rates associated with both procedures were extraordinarily low, according to Dr. Brott, and the outcomes were the best ever reported in a randomized trial that evaluated these outcomes.
Of note, physicians participating in CREST had to undergo a credentialing process in which level of experience and rates of complications and death for both endarterectomy and stenting had to meet rigorous study criteria.
Because stenting is less invasive than endarterectomy, it might appear to be the better option for older patients, who may be frail and have multiple comorbidities. The study, however, found that the opposite was true. Patients older than 70 years had better outcomes with endarterectomy and those younger than 70 years fared marginally better with stenting.
These findings could be explained in part by the often deteriorated state of blood vessels in people older than 70 years. As Dr. Brott points out, "Vascular tortuosity and calcification in areas other than the site of the procedure may play a role. In contrast, during endarterectomy, the surgeon interrupts the blood flow below and above the area of narrowing and is not challenged by plaque in other parts of the arterial system."
Harry Cloft, M.D., Ph.D., a neuroradiologist who participated in the study at Mayo Clinic in Minnesota, adds that elderly patients may also be less able than younger patients to form a vascular bypass through collateral circulation in response to a plaque-based occlusion. The researchers are now examining the angiograms of the study population to see if vascular health is associated with poorer outcomes for stenting in patients older than 70 years.
"All good research leads to more questions," says Dr. Cloft. Bart M. Demaerschalk, M.D., a vascular neurologist and CREST site principal investigator at Mayo Clinic in Arizona, notes that although endarterectomy has been shown to reduce stroke risk 10 years post-procedure, a question arising from the CREST results is the long-term durability of stenting.
The National Institutes of Health is funding a 10-year follow-up study to compare the long-term outcomes of both procedures, starting this year. The multi-institutional study will again be led by Dr. Brott at Mayo Clinic in Florida.
The CREST findings highlight the advantage of treating carotid stenosis with a multidisciplinary team approach in which all options are considered.
At Mayo Clinic in Arizona, for example, patients were historically seen by a vascular neurologist, a neurosurgeon, a vascular surgeon or an endovascular surgical neuroradiologist. Once CREST began, the vascular experts across subspecialties made it mandatory that all patients with carotid stenosis be seen by a member of each subspecialty. The subspecialists then met as a team to assess a patient's candidacy for CREST.
This practice continues today and includes all patients, regardless of candidacy for CREST. Every patient with carotid stenosis is assessed by a collaborative team that includes a neurologist, a vascular surgeon or neurosurgeon, and an endovascular surgical neuroradiologist — an approach used at all three Mayo sites.
"We rallied around the trial and wove our research into our clinical practice to best serve our patients," says Dr. Demaerschalk. "CREST has shown that both endarterectomy and stenting are safe and effective means of treating carotid artery disease. Patients are well informed before they come to us," he adds. "They know there are different options, and a team approach removes any perception of potential operator bias."