ARTICLE IN BRIEF
In a meta-analysis, the rates of stroke or death following stenting were three times higher than after angioplasty. In a retrospective review of cases from three centers, the rate of adverse events tended to be higher after stenting than with angioplasty.
CHICAGO—Intracranial angioplasty seems to be as good as, or even superior to, stenting in two papers that even the authors interpreted cautiously.
The papers, a meta-analysis of previously published literature and a retrospective review of outcomes at three tertiary care centers, were presented at the AAN meeting here in April, but continued to generate controversy well into the summer.
In the meta-analysis, the rates of stroke or death following stenting were three times higher than after angioplasty. In the retrospective review of cases from three centers, the rate of adverse events tended to be higher after stenting than with angioplasty. [See “Retrospective Review: University of Iowa” and “Meta-Analysis: University of Minnesota” for more data.]
Two of the University of Minnesota neurologists who authored the studies conceded that publication bias in prior studies, and possible selection bias in the three-center data, mean that the results should be taken with a grain of salt — but how big a grain is where they and some other neurologists parted ways.
Until a randomized trial proves otherwise, the co-authors of the papers said, interventional neurologists should assume that intracranial stenting or angioplasty are more or less equivalent.
“A direct comparison trial of the two modalities is warranted,” said Robert Taylor, MD, assistant professor of neurology, neurosurgery, and radiology at the University of Minnesota. But until such a trial is published, he added: “Our data are reassuring because many people have thought that angioplasty alone is not good enough. Based on this data, you may not have to use a stent. Both practice patterns are now probably acceptable until we get more data.”
THE CASE FOR STENTS
While some interventional neurologists supported that view, others said that a randomized trial between the two approaches is unlikely to be conducted any time soon, in part because the case for stenting, based on experience in other vessels throughout the body, has appeared so strong.
“In virtually every blood vessel of the body, stenting is better than angioplasty,” said Seemant Chaturvedi, MD, professor of neurology and director of the Wayne State University Detroit Medical Center Stroke Program. “It's better in preventing re-stenosis. I don't think there would be much support in the scientific community for just angioplasty, because of the problems that have been seen with re-stenosis in other vessels in the body.”
Dr. Chaturvedi is on the steering committee of the Stenting and Aggressive Medical Management for Preventing Stroke in Intracranial Stenosis (SAMMPRIS) trial now getting under way, in which patients will be randomly assigned to receive either a Wingspan stent or to receive aggressive medical management.
“The collective wisdom of these people involved with SAMMPRIS is that stenting is the way to go,” Dr. Chaturvedi said in a telephone interview.
Following Dr. Taylor's presentation of his meta-analysis data at the AAN meeting here, another neurologist speaking from the floor of the meeting room said published studies on angioplasty have been far less rigorously designed than were stenting studies.
In response, Dr. Taylor agreed that the results of the meta-analysis might be skewed by a large study, published in April 2006 in the journal Stroke, showing remarkably good outcomes for angioplasty. [See “Outcomes: Stroke 2006 Study.”]
A CALL FOR HEAD-TO-HEAD TRIALS
Other neurologists, however, said that a trial comparing intracranial stenting to angioplasty is justified, and that stenting should not be seen as absolutely necessary until proved in a head-to-head trial.
“There is a place for the SAMMPRIS study, but also for one comparing stenting to angioplasty,” said James C. Grotta, MD, professor and chair of neurology at the University of Texas Medical School and director of the stroke program at Memorial Hermann Hospital in Houston. “These two new studies are definitely of interest and bring up a big problem in unraveling the role of endovascular treatment of intracranial disease, namely that the technology for endovascular treatment is still evolving.”
However justified a trial between the two modalities might be, finding the necessary funds and selecting the balloon brand, size, and exact procedure for angioplasty will be difficult, according to one of the neurologists who sat on the panel during which the meta-analysis was presented.
“If you could do angioplasty and not leave behind a foreign body and get the same or superior results to aspirin, that would be important to know,” said Wade S. Smith, MD, PhD, director of neurovascular services at the University of California-San Francisco. “But there are two main problems. First, standardizing the procedure is hard. There aren't particular balloons designed specifically for intracranial angioplasty. People have been using different balloons, different sizes, different inflation times.”
The second problem, Dr. Smith said, is funding a trial. “The companies that make the balloons probably wouldn't have tremendous interest, because these are relatively inexpensive devices for a procedure that is relatively uncommon,” he said. “The NIH could fund it, but they have limited dollars, and the question is whether they'd consider it of value.”
In the meanwhile, he said, “I remain skeptical that angioplasty is going to be better than stenting. I have a hard time, based on the coronary model, coming to that conclusion. It's a great question to ask, it's important to try to answer if we can, but I worry that it would be impractical to actually answer.”
But a co-author of the two new papers said that evidence gained from coronary stenting studies is not sufficient to prove the value of the devices in the brain.
“We have assumed that because stent placement was superior to primary angioplasty in the coronary circulation, it would be superior in the intracranial circulation,” said Adnan I. Qureshi, MD, associate head of neurology and professor of neurology, neurosurgery and radiology at the University of Minnesota. “The new evidence advises us to bear caution prior to making such assumptions. There are enough differences between the pathology of the two circulations that it is not unreasonable to consider the possibility of different results for the same technology.”
Although the main benefit of stenting is in preventing re-stenosis, Dr. Qureshi added, “Our data suggests that most re-stenosis following intracranial angioplasty is asymptomatic. This has to be counterbalanced with the higher technical challenges of stent placement and cost associated with it. It may still be that stent placement is superior after all in the intracranial circulation. However, that inference should not be made without a rigorous scientific evaluation.”
META-ANALYSIS: UNIVERSITY OF MINNESOTA
* Investigators compared the results of 12 previously published reports of primary angioplasty, involving 233 patients followed for a total of 5,569 months, against 23 for stent placement, comprising 706 patients followed for 5,292 months.
* They counted 24 stroke events and 34 stroke-or-death events following angioplasty, and calculated the rates of stroke and stroke-or-death as 3.6 and 5.1 per 100 patient-years, respectively.
* By comparison, they counted 71 stroke events and 104 stroke-or-death events following stenting, and calculated the rates of stroke and stroke-or-death as 11 and 16.3 per 100 patient-years, respectively.
RETROSPECTIVE REVIEW: UNIVERSITY OF IOWA
* Investigators analyzed clinical and angiographic data on 190 patients treated with 98 intracranial stents and 95 angioplasty procedures in three tertiary care centers.
* More than 50 percent residual stenosis occurred following 14 out of 94 angioplasties (15 percent) and four out of 96 stenting procedures (4.1 percent), which was a statistically significant difference (p=0.01).
* There were no significant differences in fatalities or strokes during the periprocedure period or during a mean follow-up of 20.8 months. But there appeared to be a trend toward increased risk of combined endpoints of stroke and death in the stent group (8 in angioplasty and 10 in stent-treated group, p=0.09) after adjusting for age, sex, location, and post-procedure stenosis.
OUTCOMES: Stroke 2006 Study
* 120 patients with 124 intracranial stenoses were treated by primary angioplasty. All patients had neurologic symptoms (stroke or transient ischemic attack) attributable to intracranial stenoses greater than 50 percent.
* There were three strokes and four deaths (all neurological) within 30 days of the procedure, giving a combined periprocedural stroke and death rate of 5.8 percent.
* At a mean follow-up time of 42.3 months, six patients had a stroke in the territory of treatment and five additional patients with stroke in other territories; 10 deaths occurred, none of which were neurological.