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Two observational studies of intracranial stenting in patients with symptomatic stenosis show relatively low complication rates and a small but ongoing risk of recurrent stroke out to 6 months. Overall, the papers, both published online June 2, 2011, ahead of print in Stroke, suggest that revascularization using a novel intracranial stent system compares favorably with medical therapy for this high-risk group.

However, the recent announcement that a randomized trial of the 2 strategies was halted prematurely due to a nearly 3-fold higher rate of periprocedural events with stenting cast a shadow over the new data, and prompted calls to carefully review them for lessons in improving patient selection and stenting technique.

A Single-Center Experience

In the first study, investigators led by Wei-Jian Jiang, MD, of Beijing Tiantan Hospital (Beijing, China), looked at 100 consecutive patients who had symptomatic intracranial atherosclerotic disease with at least 70% stenosis and underwent elective stenting within 90 days of a minor stroke or TIA at their institution between January 2007 and February 2009. All patients received the self-expanding nitinol Wingspan stent system (Stryker, Fremont, CA).

This cohort’s periprocedural and longer-term outcomes were compared with those of a subgroup of 206 similar patients who received medical therapy in the WASID (Warfarin and Aspirin for Symptomatic Intracranial Atherosclerotic Disease) trial.

Stents were successfully placed in all but 1 patient. During a follow-up of 21.4 ± 8.2 months, the primary endpoint, a composite of any stroke or death within 30 days or ipsilateral stroke anytime thereafter, occurred in 9 patients: 5 strokes within 30 days (including 3 ischemic strokes and 2 intracerebral hemorrhages, none of which were fatal) and 4 strokes after 30 days. The cumulative probability of the primary endpoint at 1 year was 7.3% (95% CI 2.0-12.5), which compared favorably with the 1-year risk of ipsilateral stroke in the historical controls (18%; 95% CI 13-24; P < 0.05).

In addition, 7 TIAs and 2 emergency cerebral artery revascularizations occurred during the first 30 days, while 6 patients experienced TIAs in the territory of the stented artery after 30 days.

At a mean follow-up of 8.6 months, 45 stented vessels in 44 patients were evaluated by angiography, revealing in-sent restenosis in 12 vessels, just under half of which were symptomatic.

After stenting, all patients were given aspirin and clopidogrel for 3 to 36 months. In addition, appropriate use of antihypertensives, lipid-lowering agents, and insulin or oral hypoglycemics helped achieve improved risk factor control at last follow-up.

The authors conclude, “These findings indicate that the rate of ipsilateral ischemic stroke after 30 days of [intracranial atherosclerotic] stenting is low and relatively constant, and the most important quality control in clinical practice or trials of [intracranial atherosclerotic] stenting is to reduce periprocedural major complications.”

Insights from Long-term Registry

One-year follow-up from the US Wingspan Registry, meanwhile, shows results comparable to those of the Chinese study. In addition to evaluating the durability of the Gateway-Wingspan stenting system, an important goal of the registry study was to identify contributors to ischemic events after successful stenting.

Over 21 months, a team headed by David J. Fiorella, MD, PhD, of Stony Brook University Medical Center (Stony Brook, NY), stented 158 patients with 168 intracranial lesions at 5 participating centers in the United States. The average treated stenosis measured 75.2%, and the majority (69%) were over 70%.

The average follow-up was 14.2 months. Cumulative rates of the primary endpoint (a composite of stroke or death within 30 days or ipsilateral stroke after 30 days) were 15.7% for all patients and 13.9% for those with high-grade (70%-99%) stenosis.

Nine patients (5.7%) suffered a stroke during the periprocedural period, and 4 (2.5%) died as a result. After 30 days, 13 patients experienced ipsilateral strokes, 3 of which resulted in death. Ten of those events occurred within 6 months and none after 1 year. An additional 9 patients had an ipsilateral TIA after 30 days, yielding a 20% combined rate of stroke or TIA between 30 days and 12 months.

Dual antiplatelet therapy was typically continued for 3 to 6 months, with clopidogrel discontinued if angiographic follow-up showed no in-stent restenosis.

Importantly, among the 13 ipsilateral ischemic strokes, 5 were judged to be due to in-stent restenosis and occurred at an average of 6.9 months postprocedure, while 5 were attributed to disruption of antiplatelet medication and occurred at an average of 4.4 months after stenting. Among the 9 ipsilateral TIAs after 30 days, 7 events were associated with in-stent restenosis and 1 with interruption of antiplatelet drugs. One case each of stroke and TIA was linked to both factors.

An important limitation of this analysis, the investigators acknowledge, is that 13% of eligible patients were not available for 12-month follow-up, and it is unknown whether event rates in that group would be similar to those of the rest of the study population.

However, they write, “The present data suggest that if patients with [in-stent restenosis] do not become symptomatic during [the] initial 3- to 6-month period after [successful stenting] and an appropriate medication regimen is maintained, it is unlikely that they will ultimately become symptomatic in follow-up.”

SAMPRISS: Setback or Spur to Progress?

In an editorial accompanying the 2 studies, Alex Abou-Chebl, MD, of the University of Louisville School of Medicine (Louisville, KY), notes that the new findings “have to be viewed in the context of a post-SAMMPRIS world.” The randomized SAMMPRIS trial, which was evaluating aggressive medical management with or without angioplasty and stenting in patients with high-grade symptomatic intracranial stenoses, recently was halted due to a 30-day rate of stroke or death of 14% with stenting compared with 5.8% in the medical arm. That rate is almost three-fold higher than in the current studies.

However, Dr. Abou-Chebl adds, this setback provides an opportunity to look at the shortcomings of current data on intracranial stenting and address issues that will promote more rigorous evaluation of the therapy, such as better identifying which patients fare best with medical therapy vs. endovascular intervention and applying knowledge gained from endovascular treatment of CAD to intracranial stenting.

Commenting on the demise of SAMMPRIS to TCTMD, L. Nelson Hopkins, MD, of University at Buffalo Neurosurgery (Buffalo, NY), a coauthor of the Wingspan registry paper, recalled that the trial was developed to test the Wingspan stent almost as soon as the new technology became available.

The problem, he said in a telephone interview, is that many centers were recruited to ensure adequate numbers of patients and the operators were still very early in the steep learning curve for use of the Wingspan stent. “So the results were not as good as we would have anticipated if there had been a more stable technology and technique,” he observed.

“The distressing part is that when third-party payers see data like this and the trial stopped early, they think that the technology is no good,” Dr. Hopkins added. “But that’s not the case at all. And the disease we’re dealing with is extremely serious. If a patient has a 70% stenosis and is symptomatic, the 1-year morbidity and stroke rate with medical therapy is well over 20%. So we simply have to find better ways to deal with the disease. The upside of the SAMMPRIS experience is that we will get a lot of interesting data that will help us progress with the technology.”

Learning Who Not to Stent

More specifically, Dr. Hopkins said, “if we look carefully at all of the complications in the SAMMPRIS trial, we will definitely learn something about who not to stent. [For example,] I think if you have a long, irregular stenosis, the results are not going to be anywhere near as good as with a shorter, focal stenosis. But we’ll have to wait and see. And it may be that we should be thinking in terms of a limited procedure—angioplasty-only initially, then carefully following the patient and putting in a stent only if the stenosis comes back. In complex lesions, it may well be that angioplasty alone is a much safer procedure.”

One of several unanswered questions about technique is whether to postdilate the self-expanding Wingspan stent in order to optimize apposition and thus potentially reduce the risk of stent thrombosis and early restenosis. Dr. Abou-Chebl comes down in favor of the approach. Dr. Nelson, however, was less certain. “My problem is that if you have an irregular stent-plaque interface, you’re going to have a higher rate of complications and of restenosis,” he noted, adding that a balloon-expanding stent such as the device used in the randomized VISSIT trial (Pharos; Micrus Endovascular, San Jose, CA) may be “a better way to go.”

Dr. Hopkins noted that new options such as drug-eluting balloons and drug-eluting stents also “are potentially going to be important in the intracranial circulation.”

But for now, he concluded, “What we need is more patients treated, more data, and more experience among operators to reduce the risks.” 

 

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Sources:
1. Jiang W-J, Yu W, Du B, et al. Outcome of patients with ≥ 70% symptomatic intracranial stenosis after Wingspan stenting. Stroke. 2011;Epub ahead of print.
2. Fiorella DJ, Aquilla ST, Levy EI, et al. US Wingspan registry: 12-month follow-up results. Stroke. 2011;Epub ahead of print.
3. Abou-Chebl A. Intracranial stenting with Wingspan: Still awaiting a safe landing. Stroke. 2011;Epub ahead of print.

 

 

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