This study provides preliminary postmarketing multicenter data on the experience with the Wingspan stent in patients with 70% to 99% symptomatic intracranial stenosis. Compared to the Wingspan Phase I study of patients with 50% to 99% stenosis,31
the use of the Wing-span stent in this registry was associated with a similar high rate of technical success but higher rates of restenosis and stroke or death within 30 days of stenting.
The high technical success rate (96.7%) in this study, even in arteries that have been challenging to stent previously (e.g., the MCA), is probably related to the very flexible design of the Wingspan stent and the fact that the Wingspan system is an iteration of the Neuroform stent (BSC, Fremont, CA) which most neurointerventionalists have experience with in treating cerebral aneurysms.32
Other studies involving experienced neurointerventionalists have also shown similar high technical success rates associated with the use of the Wingspan stent.29,31,33
These high rates of technical success may not be reproducible by less experienced interventionalists with little Neuroform or cerebral microcatheterization experience.
The deliverability of Wingspan, a flexible self-expanding stent, is in contrast to the deliverability of coronary balloon-mounted stents which have been used off-label in the intracranial circulation.16,17,19–25,27
In a report of 59 patients treated with drug-eluting balloon-mounted coronary stents, 50% of the patients had lesions in the extracranial vertebral artery, 8% were in the intracranial internal carotid artery, and none were in middle cerebral artery, reflecting the difficulty in tracking the coronary stents into the intracranial circulation.34
The rate of restenosis in this study is higher than the rate in the Wingspan Phase I study (7.5% at 6 months). The reasons for the higher rate in this registry are uncertain but it is possible that our restenosis rate may be an overestimate of the true rate since selection bias may have influenced who underwent reimaging (<50% of our patients underwent reimaging). However, it is also possible that the Phase I study may have underestimated the true rate of restenosis associated with the Wingspan stent.
Intraprocedure technical factors (size and location of stented artery, residual stenosis poststenting) and postprocedure medical factors (e.g., control of vascular risk factors, duration of combined anti-platelet therapy with aspirin and clopidogrel) will need to be monitored and correlated with the risk of restenosis, especially symptomatic restenosis, in future stenting trials. The risk of stroke associated with restenosis after stenting of an intracranial artery has not been well studied, however, the risk of stroke associated with restenosis after extracranial carotid stenting appears to be low.35
This is probably related to the fact that restenosis within the first 6 months of stenting is usually due to neointimal proliferation rather than recurrent atherosclerosis. Neointimal proliferation results in a smooth endothelial surface which is less likely to ulcerate or produce turbulent flow and distal embolization than atherosclerotic stenosis.35,36
The rate of stroke or death within 24 hours in this study of patients with 70% to 99% stenosis was 6.2% and is similar to the periprocedural rates of stroke or death in two other Wingspan series of symptomatic patients with 50% to 99% stenosis (6.1% to 6.7%).29,33
At 30 days, the rate of stroke or death in patients in this registry was 9.6% which is higher than the 30-day rate of stroke or death in patients with 50% to 99% stenosis treated in the Wingspan Phase I trial (4.4%). Based on the lower 30-day rate of stroke and death at our high enrolling sites vs low enrolling sites, we anticipate that the overall 30-day rate of stroke or death will diminish as more experience with the Wingspan stent accumulates. Additionally, with careful selection of interventionalists in future trials and the use of aggressive statin therapy before stenting, which has been associated with a lower periprocedural risk of stenting in patients with extracranial carotid stenosis,37
a lower 30-day rate of stroke or death after stenting with Wingspan in patients with 70% to 99% stenosis is possibly achievable in future studies.
The rate of any stroke or death within 30 days or stroke in the territory beyond 30 days (the anticipated primary endpoint in a randomized trial of stenting vs medical therapy) was 14.0% at 6 months which is similar to the 6-month rate of this endpoint in WASID patients with 70% to 99% stenosis.9
However, at high enrolling sites in this registry, the primary endpoint rate at 6 months was 9.5%. This rate is similar to the rate of stroke in a study of patients with 70% to 99% stenosis treated with intracranial stenting at a high-volume center in China.19
Since patients with 70% to 99% stenosis and TIA or stroke within the previous 30 days are at highest risk of stroke, they stand to gain the most from stenting. Therefore, in the randomized trial of stenting vs medical therapy we are planning, these are the patients who will be targeted for enrollment. Comparison of the Kaplan-Meier curves () for the patients in WASID vs the patients in this registry with these high-risk features suggests that the curves are similar in the first 90 days and then diverge in favor of stenting beyond 90 days. However, the wide CIs around the primary endpoint rate in the stenting arm do not rule out that stenting could lower the risk of the primary endpoint by as much as 50% or may have no benefit over medical therapy.
This study has several limitations. It was not designed as a prospective clinical trial and therefore does not have many of the rigorous design features of such a trial, e.g., prospective collection of data in all patients, rigorous data auditing, a protocol specified evaluation by a neurologist before and after the procedure, central adjudication of events and angiogram readings, more rigorous inclusion and exclusion criteria, and a prespecified protocol for the stenting procedure and concomitant medical therapy. Additionally, the small number of patients followed beyond 6 months makes the estimation of event rates 6 to 12 months after stenting imprecise.
Despite these limitations, this study provides important preliminary data on the technical success of stenting and outcome of patients with 70% to 99% intracranial stenosis treated with the Wingspan stent. Whether stenting with Wingspan provides any benefit compared with medical therapy in these patients can only be established in a randomized trial which we are planning.