Highest-Risk Patients With Intracranial Stenosis Have Unmet Need

January 19, 2016

New approaches to treatment are urgently needed for patients who have had a recent stroke or transient ischemic attack  attributed to intracranial arterial stenosis and are at the highest risk for a repeat stroke, a new analysis of the SAMMPRIS (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) trial suggests.

The main SAMMPRIS trial results, published in the New England Journal of Medicine in 2011, showed that aggressive medical therapy was more effective than stenting for preventing stroke in patients with symptomatic intracranial stenosis. However, the risk for stroke or death was still high in the medical group: 15% during a median follow-up of 32.7 months.

The current analysis, published online in JAMA Neurology on January 4, was aimed at identifying factors that were associated with a particularly high risk for a repeat stroke in the medical group.

Results showed that those at highest risk were significantly more likely to have stroke as the qualifying event for the trial, an old infarct in the same territory, and no statin use at enrollment.

The authors, led by Michael F. Waters, MD, University of Florida College of Medicine, Gainesville, conclude that "the features identified in this analysis will be useful for choosing eligibility criteria for future trials focused on novel therapies for improving the outcome of high-risk patients with intracranial stenosis."

Dr Waters commented to Medscape Medical News that the main result of SAMMPRIS — that patients in the medical group did better than those who underwent stenting — was a complete surprise. "But this could have been due to procedural complications with the stenting as there is always the possibility that we can make things worse with interventions," he said.

"However, even though the medical group did better, there was still a high rate of repeat stroke in this group. We know these patients are at very high risk. This substudy is looking at trying to identify factors associated with a very high risk of repeat stroke where a different approach may be needed."

He added: 'We were able to identify a couple of risk factors associated with very high risk, such as evidence of a previous stroke in the same territory. This was present in about 30% of patients."

"We would like to use this data to draft a proposal for another clinical trial in the subset of patients at very high risk for repeat stroke. Medical management did not reduce risk to less than 1 in 3 for these patients. Medical therapy is not going to cut it for them."

The current post hoc analysis of the SAMMPRIS trial focused on the 227 patients in the medical group.

The initial analysis found several factors associated with increased risk for repeat stroke or death, but after multivariable analyses three remained significant.

Table. Factors Associated With Increased Risk for Stroke or Death in SAMMPRIS Medical Group

Factor Hazard Ratio (95% Confidence Interval) P Value
Old infarct in same territory 2.6 (1.3 - 5.3) .006
Stroke as qualifying event 3.0 (1.1 - 1.7) .03
No statin use at time of enrollment 2.4 (1.1 - 5.2) .03

 

"In spite of best medical management there is a subset of patients at very high risk of repeat stroke," Dr Waters commented. "We desperately need better treatments for this cohort."

In patients with a stenotic artery, if they have had a previous stroke at this site and an 80% stenosis, then something besides aggressive medical therapy is needed, he added. "If I knew that I had a 1 in 3 chance of a repeat stroke I would like something else."

Dr Waters noted that because of the main SAMMPRIS results, there has been a moratorium on using stents in patients with intracranial stenosis. "But this shouldn't mean that endovascular therapy is out to dry," he said.

"I think it is still worth investigating interventional approaches in this very high-risk group. Look what's happened with in acute stroke — endovascular therapy failed so many times but now it is standard of care. As technology improved so did the benefits. We might be able to achieve the same thing in this field."

Dr Waters noted that he is involved in the "early planning stages" of a trial with a new-generation stenting technology for these very high-risk patients.

"Even though we knew the right answer at the time of SAMMPRIS, if we do find a new technology that works for the highest-risk patients it is possible that it could also be used in a lower-risk population in time," he suggested.

This study was funded by a research grant from the US Public Health Service National Institute of Neurological Disorders and Stroke (NINDS). In addition, the following Clinical and Translational Science Awards, funded by the National Institutes of Health (NIH), provided local support for the evaluation of patients in the trial: Medical University of South Carolina, University of Florida, University of Cincinnati, and University of California, San Francisco. Stryker Neurovascular (formerly Boston Scientific Neurovascular) provided study devices and supplemental funding for third-party device distribution, site monitoring, and study auditing. This research was also supported by the Investigator-Sponsored Study Program of AstraZeneca, which donated rosuvastatin (Crestor) to study patients. INTERVENT provided the lifestyle modification program to the study at a discounted rate. Walgreens pharmacies provided study medications, except rosuvastatin, to patients at a discounted price (paid for by the study). The PACE self-assessment forms for physical activity and smoking cessation were provided by the San Diego Center for Health Interventions LLC. Dr Waters and coauthors Dr Turan, Dr Chimowitz, and Mr Lynn reported receiving grant funding from the NIH/NINDS. Dr Turan also received a K23 grant from NIH/NINDS unrelated to this project.

JAMA Neurol. Published online January 4, 2016. Abstract

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