BARCELONA ― Stenting of the vertebral artery ― particularly for extracranial stenosis ― can be performed with low perioperative risk and appears to be associated with a reduced recurrent stroke risk, according to results of a new study.
But the Vertebral artery Ischemic Stenting Trial (VIST) was underpowered because of withdrawal of funding midway through enrolment, and the primary endpoint did not quite reach statistical significance, leading to the recommendation that a further confirmatory trial is needed.
The VIST trial was presented by Hugh Markus, MD, University of Cambridge, UK, at the recent European Stroke Organisation Conference (ESOC) 2016.
"I do think there is a benefit from stenting the vertebral artery, but we need another trial to confirm this," he commented. "I think in some parts of the world data from this trial will be taken as evidence to perform stenting on the vertebral artery, but in other parts of the world ― such as the UK ― it will be viewed as very interesting and enough to stent certain patients, but it will not become routine care unless confirmed in another trial."
He added: "We showed there was a high risk of recurrent stroke in patients who had very recently had a stroke or TIA caused by vertebral artery stenosis and these patients had a larger benefit from vertebral artery stenting."
"We also looked at whether there was a difference as to which part of the vertebral artery was stented and we found that the benefit appeared to be greater if the beginning of the artery was stented rather than higher up within the brain ― the risk associated with stenting at the start of the vertebral artery was very low ― there were no complications at that site."
Professor Markus explained that posterior circulation stroke accounts for 20% of all strokes but has been relatively under-researched compared with carotid strokes. About a quarter of these strokes are associated with stenosis in the basilar and vertebral arteries and these patients have a high risk of recurrent stroke. This is particularly high in patients who have V4 or intracranial vertebral stenosis, he said.
He added that vertebral stenosis is often treated with stenting: "Many thousands of stents are put in worldwide, but there are little data from randomized trials on whether they are beneficial or not."
The aim of the VIST trial was to look at whether stenting on top of best medical care was better than best medical care alone for symptomatic vertebral stenosis.
The trial, conducted at 40 hospitals in the UK, enrolled patients within 3 months of posterior circulation transient ischemic attack (TIA) or non-disabling stroke and greater than 50% stenosis because of atheromatous disease. They were randomized to best medical therapy alone or with stenting. The type of stent used was left to the operator and a variety of different brands were used.
The trialists had hoped to recruit 540 patients but recruitment was slow, and as a result funding, which was provided by the Stroke Association and National Institute for Health Research (NIHR) Health Technology Assessment Programme, was withdrawn after 182 patients had been enrolled. The decision was made to continue to follow patients until they had all reached 1 year of follow up, which was in February 2016.
Baseline characteristics were generally well balanced, with 80% extracranial stenosis in both groups. But one exception was time since last symptoms, which was shorter in the stenting group (29 vs 42 days). "This suggests the stenting group might be higher risk, as we know risk is very dependent on time since symptoms," Professor Markus said.
With regard to medical treatment during follow up, there was no difference in the use of antihypertensives or statins, with most patients taking these agents, but there was a "slight excess" of antiplatelet agents in the stenting group early on, which levelled out by 6 months.
Patients were followed for a median of 3.5 (range 1–7) years. Of note, 31 patients randomized to the stenting arm did not have stenting, mainly because after angiography they were found not to have stenosis of 50% or more.
In terms of risk of the stenting procedure, of the 48 patients with extracranial stenosis who underwent stenting there were no strokes or major complications. Among the 13 patients with intracranial stenosis who underwent stenting there were two strokes (one of which was fatal).
Primary Endpoint: 60% Reduction in Stroke
The primary endpoint was any stroke during follow up. Results showed that there were 12 strokes out of 291 years of follow up in the medical group and five strokes out of 308 years of follow up in the stented group. This gave a hazard ratio (HR) of 0.40 for stenting (95% CI 0.14 - 1.13; P = .08), a trend that did not reach significance, and an absolute reduction of 25 strokes per 1000 person-years.
Professor Markus said there was an early risk in both groups but lines started to separate after 3 months. "We found that patients who received a stent had a 60% reduction in stroke risk ― this was not quite significant, but the power of the trial had been severely limited by the early stopping of enrolment."
However, after adjustment for days from last symptoms to randomization in a Cox regression model, the result became significant with a HR of 0.34 (95% CI 0.12 - 0.98; P = .046).
Also, in a post-hoc analysis confined to patients randomized within 2 weeks after the last stroke or TIA, there were eight strokes in 30 patients on medical treatment alone vs four strokes in 47 patients who received a stent, giving a HR for the primary endpoint of 0.30 (0.090 - 0.99; P = .04).
Other analyses suggested stenting may be preferable for extracranial stenosis (HR 0.37) rather than intracranial stenosis (HR 0.47), "but these are based on very small numbers," Professor Markus stated.
He noted that the results "confirm a high rate of recurrent stroke in symptomatic vertebral stenosis despite treatment with best medical therapy."
He said further studies are now required to confirm these findings, particularly in extracranial vertebral stenosis. He added that another trial could be feasible if it included many different countries, noting that one of the factors limiting recruitment in the VIST trial was that it was conducted just in the UK.
Why Different From VAST?
In an ESOC video on the study, Professor Bart van der Worp, University Medical Centre in Utrecht, the Netherlands, asks how the VIST results can be compared with those of a similar Dutch trial of vertebral artery stenting (VAST) reported last year, which showed no difference between stenting and medical treatment.
Professor Marcus replied that the VIST trial had a slightly longer follow up, which may explain the difference in the results. "A longer follow up is necessary to see benefits as the risk of stenting occur early on ― around the time of the procedure ― whereas the benefits accrue over time."
But he added that both trials were too small to give a definitive answer. "VAST only had around 100 patients, so was even smaller than VIST. Taken together I would say there probably is a benefit of stenting the vertebral artery, but we need more data to prove this."
When considering how these studies compare with trials of intracranial stenosis such as SAMMPRIS, which suggested a worse outcome with stents than best medical therapy, Professor Markus said that "looking at all the data together, there seems to be trend towards a benefit of stenting in extracranial stenosis, but not in intracranial stenosis."
The VIST trial was jointly sponsored by Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and funded by research grants from the Stroke Association and NIHR Health Technology Assessment Programme.
European Stroke Organization Conference 2016. Presented May 10, 2016.
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Cite this: VIST: Vertebral Artery Stenting May Reduce Recurrent Stroke - Medscape - May 30, 2016.