LOS ANGELES — Selected patients with severe intracranial atherosclerotic disease (ICAD) who have had strokes and in whom medical therapy failed get significant benefit from intracranial stenting when used according to approved criteria, results of a phase 4 study show.
Researchers found that 2.6% of patients treated on-label with the Wingspan Stent System (Stryker Neurovascular) had a stroke or died within 72 hours, which met the target event rate of 4% or lower.
The study suggests proper patient selection and sufficient experience on the part of interventionalists are key to successful outcomes, the trial's principal investigator, Michael J. Alexander, MD, director of the Neurovascular Center, Cedars-Sinai Medical Center, Los Angeles, California, told Medscape Medical News.
These new findings might lead to "a change in our paradigm for treatment," said Dr Alexander.
Following an interim safety analysis, the study was stopped early on October 25, 2017. The study results were released here at the International Stroke Conference (ISC) 2018.
Up to 10% of strokes in the United States are believed to be due to ICAD. An estimated 50,000 to 70,000 symptomatic cases occur every year across the country.
The Wingspan Stent System was approved to treat ICAD in 2005 by the US Food and Drug Administration (FDA) under the Humanitarian Device Exemption (HDE). The technology combines a percutaneous transluminal angioplasty balloon catheter with a self-expanding neurovascular, nitinol stent and stent delivery system.
This postapproval surveillance study — the Wingspan Stent System Post Market Surveillance Study (WEAVE) — was mandated by the FDA and funded by Stryker Neurovascular. It included 152 patients at 24 centers across the United States.
The primary objective of the study was to evaluate the rate of stroke and/or death in patients treated on-label with the Wingspan Stent System within 72 hours of undergoing the procedure.
On-label study criteria were very strict, said Dr Alexander. Patients had to be aged 22 to 80 years, have atherosclerotic disease of intracranial vessels with 70% to 99% stenosis, have not responded to medical management, and score 3 or less on the modified Rankin Scale (mRS).
They also had to have experienced two or more strokes, something that Dr Alexander believes is an "unrealistic" requirement by the FDA. Previous stent trials required only one stroke or a transient ischemic attack (TIA), he said, "but for some reason, the FDA put as part of the criteria for renewal of this approval that the patient had to have had two strokes."
That may have something to do with wanting to ensure that the procedure is "absolute salvage therapy," said Dr Alexander.
The company may request that the FDA revise this requirement, he said. "They believe this procedure is safe or safer than carotid stenting," where patients who have had no strokes are treated. He also noted that clinicians don't wait for a person to have two heart attacks before they intervene.
In addition to patients treated on-label, the analysis included 46 patients treated off-label with the stent system by the same interventionalists. Reasons for off-label use included being older than age 80 years and not refractory to medication, having had fewer than two strokes, having an mRS score greater than 3, and being 7 days or less post-stroke. Half of the off-label group was treated with the stent within a week of stroke.
The percentage of patients with stroke or death within 72 hours in the on-label group was 2.6% compared with 23.9% in the off-label group (P = .0001).
The analysis suggests that off-label use of the stent within a week of a stroke significantly increases the risk for peri-procedural stroke and death, said Dr Alexander.
In patients with ICAD, the recently infarcted area is very susceptible to bleeding, he explained.
"The junction between the capillaries and brain cells is weak because it's stroked out. If all of a sudden, you open that up and there's a lot of blood flow to that area, the risk of hemorrhaging into that area is higher."
Also, it's typical with stent procedures to first have patients take antiplatelet therapy for a week, enough time to allow it to become therapeutic, with the idea that this will help prevent a stroke.
These new results differ from those of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS).
That trial enrolled patients who had a TIA or nondisabling stroke attributable to stenosis of 70% to 99% of the diameter of a major artery. At 30 days, the stroke or death rate was significantly higher in patients randomly assigned to aggressive medical management plus angioplasty and stenting with the Wingspan Stent System than in the medical-management group (14.7% vs 5.8%; P = .002).
The probability of the occurrence of a primary endpoint over the entire follow-up period was also higher in the Wingspan group than in the medical management group (20.0% vs.12.2%; P = .009).
On the basis of the SAMPRISS results, and results of the original HDE clinical study, the FDA approved label changes in August 2012, limiting use of the Wingspan stent to patients with severe intracranial stenosis and recurrent stroke despite continued medical management but who had not had any new symptoms of stroke with the 7 days before planned implantation of the device.
"The agency's assessment of benefits and risks for this device considered that these patients are at serious risk of life-threatening stroke and have limited alternative treatment options," an FDA statement said at that time.
Consequently, neurologists were reluctant to refer patients for this procedure, "even if these patients had failed medical therapy once, twice, three times, because, in their minds, stenting didn't work." noted Dr Alexander.
But he pointed out several flaws in the SAMPRISS study. For example, the high periprocedural complication rate may have been due to the inexperience of those performing the procedure, he said.
The average number of procedures done by operators in the SAMMPRIS trial was 10 compared with 37 in the WEAVE trial and 50 in another similar trial, the China Angioplasty & Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) trial.
"Most people believe that 25 is a good barometer" to indicate adequate experience for any neurologic stenting procedure, said Dr Alexander. Inappropriate patient selection may also have led to poor outcomes in the SAMMPRIS trial, he said. Patients in that study were primarily treated off-label.
"It was not the stent that was the problem," Dr Alexander said, but rather patient selection and operator experience.
These new results from WEAVE should swing the pendulum in the other direction, he said. Improved outcomes should come "with an experienced person following the best practices that we have learned over the last 10 years."
This isn't the first time that a procedure initially thought to be ineffective was later proven to work. He referred to early mechanical thrombectomy trials that found this intervention wasn't superior to a clot-busting drug, but within 3 years, thrombectomy was included in stroke guidelines.
And stenting in the brain makes some sense, he said. "We stent every other artery in the body. We stent the carotids in the neck; we stent the brachials in the arm; we stent the coronary arteries in the heart. We stent the aorta; we stent the renal artery; and we stent the femoral. So why would it be any different in the brain?"
Although the criteria for the WEAVE trial included having an mRS score of 3 or better — so only mild to moderate disability — Dr Alexander said he would consider other patients.
"Let's say a patient has had a stroke and is in a wheelchair but can still talk. I don't know if I would rule that patient out in my clinical practice because you still need to save their speech or other important functions."
As for age, he said he doesn't discriminate "unless they have too many comorbidities or are too frail to have a treatment like this."
A stent with an updated design that will be more "user friendly" and promises to lead to even fewer complications, is on the horizon, he added.
Bo Norrving, MD, professor of neurology, Lund University Sweden, who moderated the session during which the WEAVE results were presented, commented to Medscape Medical News that the study addresses only the short-term complication rate.
"A residual issue is how the procedure compares with best medical therapy in the longer perspective," in terms of preventing strokes, said Dr Norrving.
Medscape Medical News also sought input about the study from Helmi Lutsep, MD, vice chair and Dixon Term Professor, Department of Neurology, Oregon Health & Science University (OHSU), associate director, OHSU Stroke Center, and chief, neurology, VA Portland Health Care System. Dr Lutsep was a site principal investigator for SAMMPRIS; hers had the largest enrollment of any of the trial sites.
These new results suggest that the stent procedure appeared safer than that previous trial had shown, said Dr Lutsep.
"I was impressed that there did seem to be maybe more hope for the stent than we had been saying through SAMMPRIS."
She pointed out that in SAMMPRIS, the outcome was 30-day stroke and death rate, so it may have captured outcomes for patients who "escaped" the 72-hour time frame. However, she said she believes that the 72-hour postprocedure period is "high risk."
While questions remain "for sure," Dr Lutsep said the new results "are tantalizing" and suggest that "maybe we can do better" and "choose patients more carefully."
Philip B. Gorelick, MD, professor, translational science and molecular medicine, Michigan State University College of Human Medicine, Grand Rapids, and chief medical officer, Thorek Memorial Hospital, Chicago, Illinois, was cautiously positive about the results.
"The results of WEAVE raise hope that a select group of patients with symptomatic intracranial occlusive disease can benefit from deployment of the Wingspan stent," said Dr Gorelick.
WEAVE was an FDA-mandated 522 postmarket surveillance study funded by Stryker Neurovascular. Dr Alexander is a consultant for, and a device proctor, for Stryker Neurovascular.
International Stroke Conference (ISC) 2018. Late-breaking abstract 13. Presented January 25, 2018.
Medscape Medical News © 2018
Cite this: WEAVE: Positive Phase 4 Results for Intracranial Stenting - Medscape - Feb 02, 2018.