Endovascular Stroke Treatments and IV t-PA May Have Similar Outcomes

HONOLULU—Endovascular procedures in acute ischemic stroke patients produced no incremental benefit beyond that achieved by standard treatment with IV t-PA, according to research presented at the 2013 International Stroke Conference.

The results of the first prospective, randomized study to compare the two approaches call into question what has become the standard approach at many centers to treating acute ischemic stroke, which is to move from treatment with IV rt-PA to more aggressive endovascular embolectomy devices when rt-PA fails to unblock a large intracranial artery quickly.

“This trial did not show that endovascular therapy achieves superior outcomes as compared with IV thrombolysis, and our findings do not provide support for the use of the more invasive and expensive endovascular therapy over IV treatment,” said Alfonso Ciccone, MD, a physician in the stroke unit at Hospital Niguarda Ca’ Granda in Milan.

Endovascular Therapy Is Widely Perceived As Effective
Endovascular treatments are widely used, despite scant evidence for their efficacy, noted Dr. Ciccone in an article published in the February 6 issue of the New England Journal of Medicine. “The high rate of recanalization with endovascular treatment might give the impression that this method is effective in most cases, although it may provide no clinical benefit in almost half the patients,” he said. “Physicians’ belief that interventional approaches were superior to medical treatment was a serious obstacle in organizing randomized trials in the past decade.”

Reported recanalization rates have been about 46% of patients treated with IV t-PA and more than 80% of patients treated by an endovascular procedure. Despite these reports, IV treatment with t-PA remains standard treatment for acute ischemic stroke, although more than half of the patients who receive this treatment die or have incomplete recovery.

The Local vs Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS) expansion trial randomized 362 patients with acute ischemic stroke at 24 Italian centers from February 2008 to April 2012. Among the 181 subjects assigned to IV t-PA, 178 received the treatment at a median dose of 66 mg within 4.5 hours of stroke onset and at a median of two hours and 45 minutes after stroke onset.

Among the 181 patients assigned to endovascular therapy, 165 received treatment, which included angiography, followed by intra-arterial t-PA, mechanical thrombolysis or thrombectomy, or a combination of these methods used at the discretion of each operator. Fifty-six patients received treatment with a device, including the Solitaire thrombectomy device (18 patients) and the Penumbra clot remover (9 patients), as well as other clot removal devices. Patients assigned to endovascular therapy had to receive treatment within six hours of stroke onset. The median time to endovascular treatment was three hours and 45 minutes: a full hour longer than the median time to IV t-PA.

Time to Endovascular Treatment Did Not Affect Outcomes
The study’s primary end point was the percentage of patients who were alive and free of disability 90 days after treatment, defined as a modified Rankin Scale score of 0 or 1. This outcome occurred in 30% of the endovascular patients and in 35% of the IV t-PA patients, a difference that was not statistically significant. After adjustment for between-group differences, including age, sex, initial stroke severity, and atrial fibrillation status, endovascular treatment was associated with 29% fewer good outcomes, compared with IV t-PA, a difference that was not statistically significant. All of the secondary outcomes examined also showed no statistically significant differences between the two study arms, and subgroup analyses failed to find any subgroup of patients who responded differently than the entire group did.

“The subgroup analysis suggested that the lack of superiority of endovascular treatment did not depend on the time to endovascular treatment, the stroke subtype, or the type of center,” said the researchers.

Dr. Ciccone and his associates noted that their study had not tested the hypothesis that patients selected on the basis of demonstrated vascular occlusion using noninvasive means, such as MR or CT, could incrementally benefit from the endovascular approach. They also noted that they could only test endovascular devices available between 2008 and 2012, when the study was performed, and that they had not tested the strategy of starting IV t-PA before administering endovascular intervention when needed. “Our trial hypothesis was that the disadvantage of the endovascular treatment in terms of time spent, as compared with that required by IV t-PA, might be offset by more rapid and effective revascularization achieved with the endovascular approach,” the authors said.