LOS ANGELES—A postmarketing study of the Wingspan stent shows that the safety of the device in the treatment of intracranial atherosclerotic disease (ICAD) is good enough for the device to be a reasonable alternative to medical management if the device is used on label. The data were presented at the International Stroke Conference 2018.
The results may reassure interventionalists who were concerned by results from the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, in which patients treated with the stent had a 30-day rate of stroke or death of 14.7%. The new study showed a frequency of periprocedural morbidity of 2.6%, so long as the device was used on label. Off-label use yielded a frequency of 23.9%.
“It does suggest that there may be a re-evaluation of stenting as a treatment for symptomatic ICAD, particularly in patients who have failed medical therapy, based on the safety profile we are seeing now,” said Michael Alexander, MD, Director of the Neurovascular Center and of Endovascular Surgery at Cedars-Sinai in Los Angeles, during a presentation of the Wingspan Stent System Post Market Surveillance (WEAVE) study.
Inappropriate Patient Selection?
Approximately 10% of strokes in the United States result from ICAD, and the rate ranges between 20% and 46% in China. Early trials of the Wingspan device had initial success, with complication rates of between 4.5% and 6.2%, but the SAMMPRIS trial, which directly compared stenting with aggressive medical management, showed superior outcomes with medical management. The 30-day rate of stroke or death of 14.7% was higher than that of medical therapy, which included aspirin (325 mg/day), clopidogrel (75 mg/day for 90 days after enrollment), and management of primary and secondary risk factors.
The SAMMPRIS trial may not have employed favorable patient selection. “ICAD is variable,” said Dr. Alexander. “Some patients present with hemodynamic compromise, where stenting is probably beneficial. Some present with embolic stroke, and some present with small-vessel perforator strokes that are unlikely to be responsive to stenting and better treated with medical therapy. All these patients were grouped together” in SAMMPRIS.
After the SAMMPRIS findings were published, the use of stenting declined at many US hospitals. But studies conducted before SAMMPRIS had shown much lower periprocedural morbidity, and those studies looked at on-label use of stenting. Stenting was used off label in SAMMPRIS.
The WEAVE study, which was an FDA-mandated postmarketing surveillance study of Stryker’s Wingspan stent, suggests that the off-label use of the system in the SAMMPRIS trial may explain the poor results. The SAMMPRIS protocol went beyond the approved indications for stenting by treating patients who presented with transient ischemic attacks only, patients who had failed medical therapy, and patients who had experienced a stroke in the previous seven days. In fact, about half of the patients were treated within seven days of the previous event, sometimes within 24 hours.
Previous studies had shown that risk factors for poor outcomes included stenting within 10 days of the last event, stenting a posterior circulation target lesion, stenting presentations other than stroke, and treatment at sites with a low patient volume for stenting. Patient selection is vital to success, according to Dr. Alexander. Patients with hemodynamic compromise are good candidates for stenting, while those with perforator stroke alone are better off with medical therapy. Embolic stroke patients are candidates for either approach.
WEAVE Was Halted Early
WEAVE looked at 152 consecutive patients treated on label at 24 institutions. The primary analysis group consisted of patients with a 70% to 99% stenotic intracranial atherosclerotic lesion who were refractory to medical treatment, between ages 22 and 80, and had a modified Rankin Scale (mRS) score of 3 or less at baseline. The treatment was performed at least seven days after the last stroke. Finally, patients had to have experienced two or more strokes. This last requirement presented a problem for recruitment, according to Dr. Alexander. “That was never a criterion for any of the [previous] trials, so it is not clear why FDA added [it]. That made it difficult to enroll for this trial—to have patients who had two or more strokes and still had a functional mRS score,” he said.
The study tested whether its protocol would have a periprocedural morbidity rate of 6.6%. Periprocedural morbidity was defined as a stroke or death within 72 hours.
An interim analysis at 100 patients showed that the periprocedural morbidity frequency was below 4%, which met the agency’s requirement and allowed the trial to be halted once the trial enrolled 150 on-label patients. The total number of on-label patients reached 152. The researchers analyzed the results from an additional 46 patients who were treated with stenting, despite not meeting the study’s inclusion criteria, and these patients were considered to have been treated off label. The final analysis showed that the on-label group had a rate of periprocedural morbidity of 2.6%, compared with 23.9% in the off-label group.
The most notable difference in the patient populations was that half of the off-label group received the stent within seven days of stroke. Several factors could explain the likelihood of worse outcomes when stenting is performed within seven days. “There is speculation that the plaques might be hot, and those patients might have a higher thrombotic risk with putting a foreign body in the vessel, or there is capillary instability, so reperfusing a vessel that has a 99% stenosis has a higher risk for reperfusion hemorrhage,” said Dr. Alexander.
Experience may also be a factor. Interventionalists participating in the WEAVE trial had inserted a stent using Wingspan an average of 37 times before the study began, compared with a mean of 10 times for physicians in the SAMMPRIS trial. Those who had performed more than 50 procedures had no periprocedural morbidity outcomes at all.
The study was funded by Stryker Neurovascular. Dr. Alexander has consulted for Stryker.
—Jim Kling
Suggested Reading
Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011;365(11):993-1003.