SAN DIEGO, CA — Trials of carotid artery stenting continue to provide new data, and several sessions at the last American Stroke Association Annual Meeting here were dedicated to the technique. Of particular note this year were reports about the risks of stenting in the elderly and the prevalence of solid cerebral microemboli during the procedure.
After finding that octogenarians are significantly more likely to suffer a stroke or die after carotid stenting than younger people, the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) investigators advised colleagues to “proceed with caution” when selecting older patients for the procedure.
An analysis of data from the lead-in phase of CREST showed that an increasing proportion of patients suffered stroke or death with increasing age, said CREST biostatistician George Howard, DrPH, Chair of Biomathematics and Biostatistics at the University of Alabama School of Public Health in Birmingham.
WHAT THE DATA SHOW
Reporting on the first 691 patients to undergo carotid artery stenting (as of December 31, 2003) in the trial, Dr. Howard said that overall, about 3 percent suffered a stroke or died within 30 days of the procedure. Among patients aged 80 years or older, however, nearly 11 percent suffered a stroke or died, he said. That compares with about 1 percent of patients under the age of 60, 1 percent of those aged 61 to 69 years, and 5 percent of those aged 70 to 79.
The trend for higher stroke risk with increasing age was not substantially mediated by adjustment for the symptomatic status, presence of high-risk comorbid conditions, use of a protection device, gender, or percent of stenosis, Dr. Howard said.
The findings were culled from the large database being accrued from the lead-in, or credentialing, phase of the NINDS-sponsored CREST, one of the large studies pitting carotid stenting against the gold standard of carotid endarterectomy.
During the lead-in phase, each interventionalist planning to insert a coronary artery stent during the randomization phase is required to perform up to 20 procedures to demonstrate proficiency in the technique.
“We want to ensure that the stent operators are as well qualified as the surgeons who have had years to practice,” explained CREST principal investigator Robert W. Hobson II, MD, Professor of Surgery and Program Director in the Division of Vascular Surgery at the University of Medicine and Dentistry of New Jersey in Newark.
To qualify for the lead-in phase, patients must suffer from either symptomatic disease with ipsilateral carotid stenosis of 50 percent or greater or asymptomatic disease with a stenosis of 70 percent or greater, as assessed by ultrasound or angiography. The patients are given aspirin and clopidogrel before and 30 days after the stenting procedure and examined by a neurologist pre-procedure, at 24 hours, and at 30 days.
MIXED PICTURE ON RESULTS
Despite the “disturbing” trend toward an increased complication rate with increasing age, it is too soon to conclude whether the very elderly should be offered carotid artery stenting, Dr. Howard said.
“We don't know what would have happened if they had surgery,” he explained. “It could be an 11-percent complication rate is low. Maybe 30 percent would have had a stroke or died if they had carotid endarterectomy.”
Dr. Hobson noted that “the literature shows a mixed picture; some studies show the risks of carotid endarterectomy increasing with age, some don't.” And both of the two largest studies of the procedure – the Asymptomatic Carotid Atherosclerosis Study and the North American Symptomatic Carotid Artery Trial – excluded patients over 80 years, he added.
For now, the investigators have decided it would be unethical to continue enrolling octogenarians in the lead-in phase, because there is no known advantage. Since there is no comparison group getting carotid endarterectomy, nothing can be learned, Dr. Howard explained.
But “it is equally important that we include them in the randomization phase of the trial,” Dr. Howard said. “Only by comparing the two procedures back to back can we answer the question of whether stenting is as good as or better than carotid endarterectomy.”
The bottom line: “Be cautious about selection of elderly Americans for stenting,” Dr. Hobson said. “But it is especially important that we include the elderly in this trial.”
Pierre Fayad, MD, Chairman of the Department of Neurological Sciences at the University of Nebraska Medical Center in Omaha, who was not involved in the trial, agreed. “Some studies have shown that older individuals who undergo carotid endarterectomy have a higher risk of stroke than younger people,” he said. “But at the same time, they benefited more from the procedure because we could lower that risk so much more.” Whether the same will be true for stenting remains to be proven. “But certainly we should not shut that door before we investigate the possibility,” Dr. Fayad said.
EMBOLIZATION OF PLAQUE
In a separate study, German researchers reported that there is no correlation between the embolization of plaque and thrombotic material into the peripheral cerebral vascular bed during stenting and the incidence of ipsilateral ischemic lesions.
The finding is noteworthy in suggesting that embolic protection devices designed to catch the loose pieces of plaque dislodged during stenting are unnecessary, said chief investigator Michael Rosenkranz, MD, of the Department of Neurology at the University of Hamburg.
“Carotid artery stenting may be associated with clinically silent ischemic lesions of the brain, which had been assumed to indicate the occurrence of microemboli during the procedure,” he explained.
To test that assumption, his team sought to correlate the prevalence of solid cerebral microemboli during carotid stenting with the incidence of ischemic brain lesions, as detailed by MRI.
To determine the prevalence of microemboli, they performed multifrequency transcranial Doppler in 27 consecutive patients with symptomatic high-grade carotid artery stenosis who were undergoing carotid artery stenting. High-intensity transients in the sonogram are presumed to arise from microemboli.
Of the nearly 4,300 microembolic signals detected, about 63 percent were classified as solid microemboli; the others were presumably harmless gaseous microemboli, he said. MRI revealed new ischemic brain lesions in 30 percent of patients.
But there was no association between the solid microemboli and the brain lesions, Dr. Rosenkranz said. “The incidence of ipsilateral ischemic brain lesions that follow unprotected carotid artery stenting is independent of the number of solid microemboli during the procedure.” Dr. Rosenkranz said that data did not support a clinical benefit from using the protection device.
Dr. Fayad, who led the SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) trial, the first randomized multicenter study comparing the safety and efficacy of carotid artery stenting plus embolic protection with carotid endarterectomy, disagreed.
Dr. Fayad noted that many neurologists do not believe that emboli monitoring “tells us everything about what is happening clinically.” Ischemic brain lesions are not always caused by distant emboli, but could be due to dissection for example, he said.
But more important, large randomized trials point to a clinical advantage for the use of embolic protection devices, Dr. Fayad said. Thirty-day results of SAPPHIRE showed carotid artery stenting with distal embolic protection appears to have significant results in reducing the risk of death, stroke, or myocardial infraction in high-risk surgical patients, when compared with carotid endarterectomy.
In addition, the results led to premature termination of the Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis trial – comparing carotid stenting with or without cerebral protection in patients with new-onset symptomatic and severe carotid stenosis (Stroke 2004;35:e18-e20). Termination was required by the safety committee because patients who had not been randomized to the arm with a protection device had a higher risk of stroke.
“The proof of the pudding is in the eating,” Dr. Fayad said. “The use of an embolic protection device reduces the risk of complications and death.”
ARTICLE IN BRIEF
✓ New data reported at this year's American Stroke Association Annual Meeting suggest stenting is risky for the elderly (aged 80 and over) and that there is a prevalence of solid cerebral microemboli during the procedure.