Stent Hazardous for Intracranial Stenosis in Second Study

March 27, 2015

Among patients with symptomatic intracranial arterial stenosis — an important cause of stroke — the use of a balloon-expandable stent was associated with worse outcomes than medical therapy alone in the VISSIT (Vitesse Intracranial Stent Study for Ischemic Stroke Therapy) study.

This is the second negative trial of endovascular therapy for intracranial arterial stenosis, following on from the SAMMPRIS (Stenting and Aggressive Medical Therapy for Preventing Recurrent Stroke in Intracranial Stenosis) trial in 2011, in which balloon angioplasty followed by stenting using the Wingspan self-expanding stent (Stryker) gave worse outcomes than aggressive medical therapy alone.

The VISSIT trial examined a different type of intracranial stent, a balloon-expandable stent (Micrus Endovascular, Codman & Shurtleff) that involves a simpler single step procedure for insertion.

Following the release of the SAMMPRIS trial results, there was an unplanned analysis of the short-term outcome in the VISSIT study. The trial was stopped early because of "a low likelihood of showing superiority of the stenting approach."

Final results, published in the March 24/31 issue of JAMA, show much higher rates of stroke or transient ischemic attack (TIA) in the stented patients compared with those receiving medical therapy alone, both at 30 days and 1 year.

Lead author, Osama O. Zaidat, MD, Medical College of Wisconsin, Milwaukee, told Medscape Medical News that he was "very disappointed" with the results. "The stented group did much worse than would be expected from historical data and the medically treated patients did much better. So both groups surprised us by what happened," he said.

Dr Zaidat pointed out that medical therapy has evolved over time and is now much better than in the past, but intracranial stenting has not fulfilled expectations.

"This may be because operators are not yet experienced in this approach. They need better skills in performing the procedure. Neither SAMMPRIS nor VISSIT included a roll-in phase to make sure operators are effective at the procedure. That may be relevant."

He also noted that there was clearly a procedural risk with stenting. "Most events happened early and there was a periprocedural hemorrhage rate of 5% at day 1. This is obviously unacceptable. "

Medical Therapy Recommended

In an accompanying editorial, Marc I. Chimowitz, MBChB, Medical University of South Carolina, Charleston, and Colin P. Derdeyn, MD, Washington University School of Medicine, St Louis, Missouri, point out that the lower-than-expected stroke rate in the medical group in VISSIT strengthens the treatment recommendations that emerged from SAMMPRIS: "patients with symptomatic intracranial stenosis should be treated with aggressive medical management consisting of antiplatelet therapy (with consideration of dual antiplatelet therapy for the first 90 days) and intensive risk factor management."

They add: "Currently, there is no proven role for endovascular therapy for any subgroup of patients with intracranial stenosis."

The VISSIT trial enrolled patients with symptomatic intracranial stenosis (70% to 99%) involving the internal carotid, middle cerebral, intracranial vertebral, or basilar arteries with a hard transient ischemic attack (TIA) or stroke attributable to the territory of the target lesion within the past 30 days.

The study was stopped after 112 patients of the planned 250 had been randomly assigned to receive balloon-expandable stent plus medical therapy (n = 59) or medical therapy alone (n = 53).

The primary outcome measure was stroke in the same territory within 12 months of randomization or a hard TIA between day 2 and 12 months. The primary safety measure was a composite of any stroke, death, or intracranial hemorrhage within 30 days of randomization or any hard TIA between days 2 and 30.

Both these endpoints occurred in more patients in the stented group than in the medical therapy group. The rate of intracranial hemorrhage in first 30 days was higher and disability scores worsened in the intervention group.

Table. VISSIT: Main Results

Endpoint Stent Medical Therapy P Value
Primary safety endpoint at 30 days (%) 24.1 9.4 .05
Intracranial hemorrhage within 30 days (%) 8.6 0.0 .06
1-year primary endpoint (%) 36.2 15.1 .02
Worsening of baseline disability score (modified Rankin Scale) (%) 24.1 11.3 .09

 

Dr Zaidat also speculated that another reason for the failure of the stenting approach could have been that the stent, while opening up the problematic artery, may have blocked a small side-branch artery.

But he is not giving up hope completely that an endovascular approach may one day be successful. He drew an analogy to the thrombectomy field in acute stroke, which had many failures before the successful trials recently reported.

"This approach failed at first but they didn't give up," he said. "Operators became more experienced and new devices were introduced and patient selection was improved and now we have success. I'm hopeful that the same will happen in intracranial arterial stenosis."

He added: "I think a new endovascular approach needs to be developed for these patients as the ones we have tested so far obviously haven't worked. The brain is a very difficult organ to access. We cannot extrapolate from experiences in the heart or peripheral vessels. We have to go back to the drawing board."

Dr Zaidat says at present patients with intracranial arterial stenosis should be treated with medical therapy alone. "But if they have another stroke despite best medical therapy I would consider an endovascular approach using balloon angioplasty on its own without a stent. There hasn't been a proper study of this approach but there have been some promising case reports."

"And I would use a smaller balloon than the caliber of the artery. Perhaps we have been aiming too high — to get the artery 80% open. This may do more harm. Perhaps we should be aiming for 60% instead."

Dr Zaidat also suggested trying to select patients who may benefit most from an endovascular approach. "We need to identify patients with vulnerable plaques in the narrowing of the artery. And we might be able to use blood markers of inflammation to identify patients with 'hot plaques'."

But in their editorial, Dr Chimowitz and Dr Derdeyn emphasize that for endovascular therapy (angioplasty alone or new stents) to have any role, multicenter pilot studies will be required to establish the safety and potential efficacy of these devices in carefully defined patient populations.

"Given the disappointing performance of intracranial stenting in both VISSIT and SAMMPRIS, it is difficult to forsee how these necessary steps will happen anytime soon," they conclude.

The trial was initiated and funded by Micrus Endovascular, which was subsequently acquired by Codman & Shurtleff. Dr Zaidat reported serving as a compensated consultant for Codman & Shurtleff.

JAMA. 2015;313:1240-1248. Published March 24, 2015. Abstract Editorial

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