Stenting for Symptomatic Intracranial Stenosis Flops Again
For patients with symptomatic intracranial stenosis, treatment with a balloon-expandable stent worsens outcomes compared with medical therapy alone, according to results from the VISSIT trial published in the March 24/31, 2015, issue of the Journal of the American Medical Association. The findings are concordant with those of the SAMMPRIS trial.
“Although the results of this trial will further reduce the enthusiasm for symptomatic intracranial stenosis stenting, potential next steps would be to identify a high-risk medical therapy subgroup,” Osama O. Zaidat, MD, MS, of the Medical College of Wisconsin/Froedtert Hospital (Milwaukee, WI), and colleagues write.
The VISSIT trial, conducted at 23 sites in the United States, 3 in China, and 1 in Europe, was stopped early after an interim analysis spurred by the failed SAMMPRIS trial. The analysis indicated futility after 112 of a planned 250 patients were enrolled.
All patients in VISSIT had symptomatic intracranial stenosis (≥70%) involving the internal carotid, middle cerebral, intracranial vertebral, or basilar arteries. They also had experienced a hard TIA—defined as a transient episode of neurological dysfunction caused by focal brain or retinal ischemia lasting at least 10 minutes but resolving within 24 hours—or stroke attributable to the territory of the target lesion within the past 30 days.
Patients were randomized to stenting with the Pharos Vitesse device (then manufactured by Micrus Endovascular) plus medical therapy (n = 59) or medical therapy alone (n = 53). Medical therapy included clopidogrel 75 mg daily for the first 3 months, aspirin 81 to 325 mg daily for the entire study, and appropriate management of individual patient risks. One stented patient was subsequently excluded because of an aspirin allergy and was not included in the analysis.
Trial operators were required to have placed an intracranial stent in at least 10 patients for aneurysm or atherosclerosis in the past year.
The stenting and medication groups (mean age 61.8 years) had similar baseline characteristics and medical comorbidities. The qualifying event was stroke in approximately 63% of patients, and the mean time from the qualifying stroke or TIA was 15.2 days in the medication group and 12.3 days in the stenting group.
Stenting Associated With More Strokes
The primary outcome was a composite of stroke in the same territory within 12 months of randomization or hard TIA in the same territory from day 2 to 12 months. This endpoint occurred more frequently in the stent group (36.2% vs 15.1%; P = .02).
A composite of any stroke, death, or intracranial hemorrhage within 30 days or a hard TIA from day 2 to 30 (primary safety measure) also occurred at a higher rate after stenting (24.1% vs 9.4%; P = .05). Individual rates of ischemic stroke, intracranial hemorrhage, and all-cause mortality were numerically higher in the stent group, while that of hard TIA was numerically lower.
Although the differences did not reach significance, patients who underwent stenting were more likely to have a disabling stroke (14.0% vs 7.1%; P = .34) and a worsening of modified Rankin Scale score (24.1% vs 11.3%; P = .09) through the first year.
Health status assessed by the EuroQol-5D was similar between groups.
Post hoc analyses showed that, had the trial continued enrolling patients, there was a less than 1% chance that stenting would have improved outcomes over medical therapy alone.
Similar to VISSIT, the SAMMPRIS trial also showed superiority of aggressive medical therapy over stenting, although that trial used a self-expanding stent (Wingspan; Stryker) rather than a balloon-expandable device.
In SAMMPRIS, “the 30-day event rates with medical therapy were nearly one-half of the reported event rates in the WASID (Warfarin-Aspirin Symptomatic Intracranial Disease) trial, and the balloon angioplasty with stenting results were nearly double the rates that were reported in prior stenting registries,” the authors note.
Similarly, there was a higher-than-expected rate of periprocedural events in the stenting group of VISSIT, which Dr. Zaidat and colleagues suggest could be due to “optimistic” assumptions about operator experience, limitations of the first-generation device, the timing of stenting, anesthesia choice, and blood pressure management.
Another similarity between VISSIT and SAMMPRIS is that medical therapy resulted in outcomes that were better than expected.
“One potential explanation [in SAMMPRIS] was the implementation of a lifestyle coach and strict control of risk factors…,” the authors write. “The present trial did not have [a] lifestyle coach and [had] no available data on the trend of risk-factor control over time; however, the baseline data showed blood pressure and lipid profile within the recommended targets. Both trials implemented short-term dual antiplatelet therapy, which has been shown to be effective in reducing the recurrent stroke rate.”
Not the End for Intracranial Stenting?
Dr. Zaidat and colleagues suggest that identifying a high-risk subset of patients who may benefit most could be a way forward for use of stenting for intracranial stenosis. Examples of potentially good candidates are those with a documented infarction in the territory while on antithrombotic therapy, vulnerable plaque, or poor collateral reserve.
But proving the efficacy of angioplasty alone or with stenting in a high-risk group would be challenging, according to Marc I. Chimowitz, MBChB, of the Medical University of South Carolina (Charleston, SC), and Colin P. Derdeyn, MD, of Washington University School of Medicine (St. Louis, MO).
“First, there was no evidence from SAMMPRIS that these high-risk groups benefited from stenting,” they write in an accompanying editorial. “The patients with the highest risk of stroke on medical therapy were also at the highest risk for stroke from stenting.”
Second, they say, parenchymal brain hemorrhage was frequent after stenting and would need to be addressed before the intervention could have a role.
“Third, the majority of the procedural ischemic strokes in SAMMPRIS were in perforator territories adjacent to the stent, presumably from ‘snow-plowing’ of plaque into the small perforator vessels during angioplasty or stent deployment, which may be difficult to prevent,” they caution.
And finally, they say, “in addition to unacceptably high procedural complications, both VISSIT and SAMMPRIS reported persistent risks of ischemic stroke in the territory beyond the 30-day perioperative period, ie, technically successful stenting was not protective against future stroke risk.”
To establish a role for angioplasty alone or with stenting, “multicenter pilot studies will be required to establish the safety and potential efficacy of these devices in carefully defined patient populations,” Drs. Chimowitz and Derdeyn conclude. “Given the disappointing performance of intracranial stenting in both VISSIT and SAMMPRIS, it is difficult to foresee how these necessary steps will happen anytime soon.”
1. Zaidat OO, Fitzsimmons B-F, Woodward BK, et al. Effect of a balloon-expandable intracranial stent vs medical therapy on risk of stroke in patients with symptomatic intracranial stenosis: the VISSIT randomized clinical trial. JAMA. 2015;313:1240-1248.
2. Chimowitz MI, Derdeyn CP. Endovascular therapy for atherosclerotic intracranial arterial stenosis: back to the drawing board [editorial]. JAMA. 2015;313:1219-1220.
- The trial was initiated and funded by Micrus Endovascular.
- Dr. Zaidat reports serving as a compensated consultant for Codman & Shurtleff.
- Dr. Derdeyn reports receiving personal fees from Microvention, Penumbra, and Silk Road and serving as an executive investigator for the SAMMPRIS trial.
- Dr. Chimowitz reports receiving an NIH grant to his institution for the SAMMPRIS trial as well as stents and payment for third-party monitoring of some SAMMPRIS sites from Stryker. He also reports receiving statins for patients in SAMMPRIS from AstraZeneca, aspirin for the WASID trial from Bayer, and warfarin for the WASID trial from Bristol-Myers Squibb.