NEW ORLEANS—The results from three major interventional stroke trials completed in 2013 do not support endovascular therapy as a treatment for acute ischemic stroke, according to an overview presented at the 2013 Annual Meeting of the American Neurological Association. These studies, however, did not examine new devices for endovascular therapy that showed promise in other trials. Investigators will continue to assess the role of endovascular treatments for acute ischemic stroke, but the ongoing research should not delay the administration of standard acute ischemic stroke therapy, said Karen C. Johnston, MD.

A fourth trial conducted in China last year suggested that clopidogrel and aspirin could reduce the rate of recurrent ischemic stroke in high-risk patients with transient ischemic attack (TIA) or minor stroke. The ongoing POINT study will examine this treatment’s efficacy in a primarily American population, said Dr. Johnston, Chair of the Department of Neurology at the University of Virginia School of Medicine in Charlottesville.

The Interventional Management of Stroke III
In the Interventional Management of Stroke (IMS) III study, researchers examined 656 patients with ischemic stroke. Participants in this phase III definitive efficacy trial were randomized to receive either IV t-PA and an endovascular procedure or IV t-PA alone. The investigators hypothesized that they would identify at least a 10% increase in favorable outcomes among patients who received the endovascular procedure, compared with those who received only t-PA, but the trial was stopped early by the NIH appointed data safety monitoring board when it reached a prespecified futility boundary.

The researchers found no difference in primary outcome, which was a modified Rankin scale score of 0 to 2, between the treatment groups. Approximately 41% of patients in the endovascular group had a favorable outcome rate, compared with nearly 39% of patients in the t-PA group. Numerous prespecified secondary analyses did not reveal differences between the treatment arms. The researchers saw no difference between groups, for example, in their analysis of the full spectrum of modified Rankin scale scores.

MR RESCUE
In the MR RESCUE trial, researchers studied 118 patients with ischemic stroke to examine whether analyzing the ischemic penumbra would help identify patients most likely to respond to an endovascular intervention. Patients were stratified by imaging that indicated the presence or absence of a substantial penumbra. Sixty-four participants were randomized to mechanical embolectomy within eight hours of stroke onset, 34 of whom had a penumbral pattern. Fifty-four participants were randomized to standard care within eight hours of stroke onset, 34 of whom had a penumbral pattern.

The researchers found no difference in outcome between the embolectomy group and the standard-treatment group. Among patients with a penumbra, participants randomized to embolectomy did not have better outcomes than participants who received standard care. Results were similar among patients without a penumbra. Safety outcomes also were similar between the endovascular and standard-care groups.

SYNTHESIS
To analyze whether endovascular intervention would be more effective than IV t-PA for the treatment of ischemic stroke, researchers studied 362 subjects in the multicenter SYNTHESIS trial. Participants were randomized to endovascular intervention within six hours or IV t-PA within 4.5 hours, and their median NIH Stroke Scale score was 13. The time to treatment was 165 minutes for the t-PA group and 225 minutes for the endovascular group. The researchers expected the treatment initiation difference and predicted that, despite the delay in treatment initiation, endovascular treatment would be superior to standard care.

As in the aforementioned trials, the investigators found no benefit of endovascular therapy. The rate of favorable outcomes in the endovascular group was approximately 30%, and the rate of favorable outcomes in the t-PA group was approximately 35%. Prespecified secondary outcome analyses and subgroup analyses did not identify differences between the treatment groups. The mortality rate was 8% in the endovascular group and 6% in the standard group.

CHANCE
Unlike the other studies, the fourth major stroke trial of 2013 did not examine endovascular treatment—and its results were positive. The CHANCE trial was a multicenter, phase III study conducted in China to compare two methods of early secondary stroke prevention. Researchers randomized 5,170 participants with TIA and minor stroke to either clopidogrel and aspirin or aspirin alone. The primary outcome was ischemic or hemorrhagic stroke at 90 days.

The recurrent stroke rate was 8.2% for the combination group and 11.7% for the aspirin group. The risk reduction was approximately 32% for the combination group. The benefit primarily resulted from the reduction of ischemic stroke. “There was no reduction in hemorrhagic stroke, myocardial infarction, or death from other cardiovascular causes,” said Dr. Johnston. Although the rate of bleeding was slightly increased in the combination group, the rate of severe bleeding was 0.2% in both groups.

—Erik Greb

Recent Trials Do Not Support Endovascular Therapy for Stroke