Interest in stenting for the treatment of symptomatic high-grade intracranial atherosclerosis may be rekindled after the results of a new trial showing lower rates of in-stent restenosis and stroke recurrence with the use of a drug-eluting stent.
The NOVA trial shows that use of a drug-eluting stent resulted in a markedly lower rate of in-stent restenosis at 1 year and a significantly reduced risk of stroke recurrence in the target vessel territory beyond 30 days compared with a bare metal stent.
The results of the trial were published online in JAMA Neurology on January 4.
“Stenting for intracranial atherosclerosis is not routine clinical practice in the Western world,” co-author of the NOVA trial, Wengui Yu, MD, University of California, Irvine, explained to theheart.org | Medscape Cardiology. “It is a very invasive procedure with little physician experience, and previous trials have shown a high risk of complications, so intracranial atherosclerosis is mostly treated with aggressive medical therapy.”
“The SAMMPRIS trial showed a 14% rate of stroke or death within 30 days of intracranial stenting. In addition, in-stent restenosis can occur in 15% to 30% of patients. These are major issues that do not encourage the use of intracranial stenting,” Yu commented. “The SAMMPRIS and VISSIT trials have discouraged the use of intracranial stenting in the US. I think they showed us that the technology and expertise were not ready yet.”
The current NOVA trial was conducted to try to address these issues with the use of a drug-eluting stent. The trial was performed in China, where there is higher rate of intracranial atherosclerosis and where intracranial stenting is used more frequently.
This is the first randomized trial comparing a drug-eluting stent with a bare metal stent in intracranial atherosclerosis, Yu noted.
The trial enrolled 263 patients with symptomatic high-grade intracranial atherosclerosis who were randomized to receive a drug-eluting stent (NOVA intracranial sirolimus-eluting stent system) or a bare metal stent (Apollo intracranial stent system).
The primary efficacy endpoint was in-stent restenosis within 1 year, defined as stenosis that was greater than 50% of the luminal diameter within or immediately adjacent to the implanted stent. This occurred in 9.5% of the drug-eluting stent group vs 30.2% in the bare metal stent group (odds ratio, 0.24; P < .001).
The drug-eluting stent group also had a significantly lower ischemic stroke recurrence rate from day 31 to 1 year, 0.8% vs 6.9% in the bare metal stent group (hazard ratio, 0.10; P = .03).
No significant difference in the rate of any stroke or death within 30 days was observed between the two groups ― 7.6% with the drug-eluting stent and 5.3% with the bare metal stent (odds ratio, 1.45; P = .46).
In terms of periprocedural complications, while these were not significantly different, the authors report an approximately 50% higher rate of intracranial hemorrhage and a twofold increase in the rate of disabling or fatal stroke in the drug-eluting stent group compared to the bare metal stent group.
“Although the differences were not statistically significant, possibly because of the low event rate, the potential risk should not be ignored. Sufficient training and strict qualification would be requisite for safe drug-eluting stent placement in the future,” they say.
“However, the very low rate of ischemic stroke after 30 days of 0.8% is pretty impressive. This is a step forward,” Yu said.
“I think these results will at least stimulate some interest to reevaluate intracranial stenting for symptomatic intracranial atherosclerosis in the US ― in patients who have had a recent TIA [transient ischemic attack] or stroke and are found to have intracranial atherosclerosis,” Yu commented.
“These patients are currently treated with aggressive medical therapy, but they still have a significant risk of stroke. In SAMMPRIS, there was a still a 10% risk of stroke after 3 years in the aggressive medical therapy group,” Yu said. “This is unacceptably high. In our current study, there was a reduction in recurrent stroke with the drug-eluting stent and a reasonably lower risk of complications compared with the SAMMPRIS trial.”
He added: “Our results are encouraging for the future. They suggest that this is not the end of the road for stenting in intracranial atherosclerosis and that drug eluting stents may have a role ― at least in selected patients.”
Yu noted that other results from the Registry Study of Stenting for Symptomatic Intracranial Artery Stenosis in China and the Wingspan Stent System Post Market Surveillance (WEAVE) trial showed rates of 2.6% to 4.3% for periprocedural complications with bare metal stents, suggesting that intracranial stenting may be safe in strictly selected patients with intracranial atherosclerotic stenosis.
He said these better results may have been due to better patient selection and timing of treatment.
“Stenting in SAMMPRIS was probably too early ― within 7 days of acute stroke. In WEAVE and NOVA, stenting was not done until at least 3 weeks later, when the patient was more stable,” he explained.
Yu noted that the next step will be a trial comparing a drug-eluting stent to aggressive medical therapy, and he is hoping to be involved in such a trial.
This study was funded by grants from the Ministry of Science and Technology of China and Sino Medical Sciences Technology. Yu has disclosed no relevant financial relationships.
JAMA Neurol. Published online January 4, 2022. Full text