Carotid artery bypass surgery gets another look: technologic advances have made it possible to identify which patients are the best candidates.
The procedure, which involves surgical anastomosis of the superficial temporal artery to the middle cerebral artery (STA-MCA), is the subject of a $21 million, 7-year trial funded by the National Institutes of Health.
The call is going out to physicians to refer patients to the centers participating in these trials.
Known as extracranial/intracranial (EC/IC) bypass, the procedure is getting its second chance to prove its effectiveness in selected patients for complete carotid occlusion because technologic advances, such as refinement of positron emission tomography, have made it possible to identify which patients are the best candidates for the procedure.
EC/IC bypass surgery has been shown in a series of small studies to normalize the oxygen extraction fraction (OEF), an important marker of impaired cerebral blood flow in patients with carotid occlusion.
Whether that translates into a decreased stroke risk is the subject of the Carotid Occlusion Surgery Study (COSS), now underway in 28 centers in the United States.
Candidates for the trial must be patients with symptomatic carotid occlusion and increased OEF on PET. To date, 169 patients have enrolled, and 38 patients have been randomized to treatment.
Enrollment in the nonblinded, controlled clinical trial has been slow, in part because few physicians knew the option of bypass surgery existed, said Colin Derdeyn, M.D, principal investigator for the Washington University site in St. Louis.
William J. Powers, M.D., the principal investigator for the overall study, called on neurosurgeons to support the trial in an appeal he made in the spring 2004 bulletin of the American Association of Neurological Surgeons.
The First EC/IC Bypass Study
STA-MCA surgical anastomosis was developed in 1967 and routinely performed on patients with carotid occlusion throughout the 1970s and mid-1980s.
However, data from the EC/IC Bypass Study showed no benefit for the prevention of subsequent stroke among 808 patients with symptomatic carotid occlusion, despite restoring blood flow to the carotid artery in 96% of cases (N. Engl. J Med. 1985;313:1191-1200).
The researchers were unable to assess whether the procedure was more appropriate for one or another group of patients based on their cerebral hemodynamics because, in the era when the trial was conducted, the technology necessary to understand and measure cerebral blood flow had not been developed, according to M. Gazi Yasargil, M.D., professor of neurosurgery at the University of Arkansas, Little Rock, who pioneered the surgical procedure.
"The time is ripe to work out a perfect indication for bypass surgery," he said.
PET has made it possible to measure OEF, a proven predictor of which patients have significantly decreased cerebral blood flow and are at increased stroke risk.
When there is unrestricted cerebral blood flow, the brain extracts about 40% of the oxygen delivered to it in the blood. Blood vessels dilate and constrict to maintain an equal OEF across the brain.
When cerebral blood flow falls because of reduced perfusion pressure, the brain increases the fraction of oxygen extracted from the blood to 70% or 80% to support normal oxygen metabolism.
This elevated OEF allows the brain to maintain normal function, but it puts patients at increased risk for stroke in the future.
Two prospective natural history studies, one conducted in the United States (JAMA 1998;280:1055-69) and the other in Japan (J. Nucl. Med. 1999;40:1992-8), have demonstrated that having an increased OEF as measured by PET is an independent predictor of future stroke in medically treated patients with symptomatic carotid artery occlusion.
Depending on the precise clinical and PET criteria used, the 2-year ipsilateral stroke rates ranged from 26% to 57% in patients with an elevated OEF, compared with stroke rates of 5%-15% in patients with normal OEF, according to Dr. Derdeyn, coauthor of the study conducted at the Edward Mallinckrodt Institute of Radiology, Washington University.
"The best information we have right now, as far as connecting an abnormality by physiologic imaging with a risk factor, is for increased oxygen extraction," Dr. Derdeyn told this newspaper. OEF is a powerful and independent predictor of stroke. "It identifies a high-risk subgroup, without question," Dr. Derdeyn noted.
Dr. Powers agreed on the importance of identifying subsets of patients most likely to benefit from EC/IC.
"It's absolutely clear that if it [EC/IC bypass] is ever going to work, there has to be some more refined selection criteria to pick out the people, number one, who would be at particularly high risk if treated with medical therapy, and number two, in whom the subsequent risk of stroke seems to be related to a problem that the bypass would fix," he told this newspaper.
COSS is based on the hypothesis that surgical anastomosis of the superficial temporal artery to the middle cerebral artery, when added to best medical therapy, can reduce subsequent ipsilateral ischemic stroke by 40% at 2 years' follow up in this highly select patient population despite perioperative stroke and death.
Investigators anticipate that the stroke rate in COSS will turn out to be 40% in the medically treated group and 24% in the surgically treated group, even taking into account a 12% perioperative stroke and mortality rate, as reported in the original EC/IC trial, said Dr. Powers, codirector of the Stroke Center at Barnes-Jewish Hospital and the Washington University School of Medicine.
Even if these reduced stroke rates are borne out by the study, EC/IC bypass surgery is unlikely to become as common as coronary artery bypass; elevated OEF occurs in only 30% of patients with carotid occlusion. The study's $21 million price tag over the next 5-7 years may prove to be money well spent if it settles the question of patient selection once and for all.
A similar trial, the Japanese EC/IC Trial (JET), is also working on the question of patient selection.
A third trial, the Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON) study, was recently funded by NIH to examine the hotly debated question of whether carotid bypass surgery affects cognitive function.
"This is a procedure that has some risk to it, and it has some appeal because it's so logical," said John Marler, M.D., associate director for clinical trials for the National Institute of Neurological Disorders and Stroke, in Bethesda, Md., which is funding the trial. "But it didn't work once before, and that needs to be thoroughly tested before we begin to use it again to prevent stroke. We need to be sure that this method of selecting patients selects patients who have a clear and obvious benefit," he said.
"I think Dr. Powers has presented reasonable evidence that this may do that, but we have to have a clinical trial to test it out."
Partial or complete carotid artery occlusion is estimated to cause 61,000 first strokes and 19,000 transient ischemic attacks each year in the United States. Endarterectomy has a proven track record for patients with a partial occlusion of the carotid artery.
However, edarterectomy is not suited for complete occlusion patients. EC/IC may offer an alternative treatment for these patients, who are now treated, sub-therapeutically, with aspirin, anticoagulants, and statins.
Physicians interested in learning more should visit www.cosstrial.org.
The Surgery in a Nutshell
The 4-hour EC/IC procedure involves surgical anastomosis of the superficial temporal artery to the middle cerebral artery.
While the patient is under general anesthesia, an incision of several centimeters is made in the scalp on the side of the head where the diseased artery is located. A branch of the superficial temporal artery, generally the anterior division, is then identified and dissected using a surgical microscope.
A small craniotomy is then made beneath the temporalis muscle. A frontal branch of the middle cerebral artery is identified and isolated.
Once a suitable location for the anastomosis is determined, temporary clips are placed above and below the site. A slit is cut into this branch, and the previously dissected and prepared superficial temporal artery is sewn directly onto this middle cerebral artery branch for an end-to-side anastomosis.
The clips are then removed and blood flow restored.
Risks of the surgery include subsequent stroke as a result of temporary occlusion of the middle cerebral artery branch, thrombosis of the bypass graft, myocardial infarction during surgery, bleeding, and infection.
A retrospective analysis of EC/IC bypass surgery performed on 67 patients from 1986 to 2000 reported a perioperative morbidity rate of 3%, with no mortality (Acta Neurochir. [Wien] 2004;146:95-101).
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|Title Annotation:||Clinical Rounds|
|Publication:||Family Practice News|
|Date:||Feb 15, 2005|
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