Endovascular stroke treatments add nothing beyond IV TPA

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No reason to favor endovascular approach

These results show that there is no reason to consider endovascular therapy as a first choice for most patients who qualify for intravenous tissue plasminogen activator (TPA), especially since endovascular therapy is considerably more costly and carries some anesthesia risk. In addition, intravenous TPA remains the only Food and Drug Administration–approved treatment for selected patients with acute ischemic stroke.

Dr. Larry B. Goldstein

Intra-arterial TPA is not FDA approved for treating stroke, and while clot-retrieval devices are approved as tools for removing clots, they are not approved as stroke treatments.

The SYNTHESIS Expansion study was adequately powered and carefully conducted. It failed to identify any subgroup of patients that seemed to benefit from endovascular treatment.

One important caveat is that there was no prescreening with MR or CT angiography to determine whether a clot was present. Patients randomized to endovascular therapy went directly for that treatment. Many centers would consider using an endovascular approach after screening patients. In addition, some patients might be treated with an endovascular approach who cannot receive intravenous TPA, such as patients who have had a recent surgical or endovascular procedure and hence cannot receive intravenous TPA because it poses a bleeding risk.

Several other exclusions for intravenous TPA exist that would not necessarily preclude an endovascular approach. The results from this study suggest that patients who undergo endovascular treatment because intravenous TPA is contraindicated have outcomes similar to patients treated with intravenous TPA.

The current study did not address the possible incremental benefit from endovascular treatment of patients with a persistent occlusion following intravenous TPA treatment. Other studies that will soon be reported have looked at this situation.

Dr. Larry B. Goldstein is a professor of neurology and director of the stroke center at Duke University in Durham, N.C. Dr. Goldstein said that he had no relevant disclosures. He made these comments in an interview.



Endovascular procedures in acute ischemic stroke patients produced no incremental benefit beyond that achieved by standard treatment with intravenous recombinant tissue plasminogen activator in the first prospective, randomized study to compare the two approaches.

The results call into question what has become the standard approach at many centers to treating acute ischemic stroke, to quickly move from treatment with intravenous recombinant tissue plasminogen activator (TPA) to more aggressive endovascular embolectomy devices when TPA fails to quickly unblock a large intracranial artery.

“This trial did not show that endovascular therapy achieves superior outcomes as compared with intravenous thrombolysis, and our findings do not provide support for the use of the more invasive and expensive endovascular therapy over intravenous treatment,” Dr. Alfonso Ciccone and his associates reported in an article published concurrent with his presentation of the findings at the International Stroke Conference on Feb. 6 (N. Engl. J. Med. 2013 [doi:10.1056/NEJMoa1213701]).

Dr. Ciccone and his coinvestigators noted how endovascular treatments had become widely used despite scant evidence for their efficacy.

“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,” wrote Dr. Ciccone, a physician in the stroke unit at Hospital Niguarda Ca’ Granda in Milan, and his coauthors in their published report. “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 intravenous TPA, and more than 80% of patients treated by an endovascular procedure. Despite this, intravenous treatment with TPA remains standard treatment for acute ischemic stroke, although more than half the patients treated that way die or have incomplete recovery.

The SYNTHESIS (Local vs. Systemic Thrombolysis for Acute Ischemic Stroke) Expansion trial randomized 362 patients with acute ischemic stroke at 24 Italian centers during February 2008 to April 2012. Among the 181 assigned to intravenous TPA, 178 actually received the treatment, at a median dose of 66 mg, within 4.5 hours of stroke onset and a median of 2 hours, 45 minutes after stroke onset.

Among the 181 patients assigned to an endovascular approach, 165 actually received treatment, which started with angiography followed by intra-arterial TPA, mechanical thrombolysis or thrombectomy, or a combination of these employed at the discretion of each operator. Fifty-six patients received treatment with a device, including the Solitaire thrombectomy device in 18 patients, the Penumbra clot remover in 9 patients, as well as other clot removal devices. Patients assigned to endovascular therapy had to receive treatment within 6 hours of stroke onset, and in the study, the median time to endovascular treatment was 3 hours 45 minutes, a full hour later than the median time to intravenous TPA.

The study’s primary endpoint was the percentage of patients who were alive and free of disability 90 days after treatment, defined as a modified Rankin score of 0 or 1. This outcome occurred in 30% of the endovascular-treated patients and in 35% of those treated with intravenous TPA, 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 produced 29% fewer good outcomes relative to intravenous TPA, 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 did the entire group.

“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,” the researchers wrote.

Dr. Ciccone and his associates acknowledged that their study did not test 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 during 2008-2012 when the study was done and that they did not test the strategy of starting intravenous TPA and then following with 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 intravenous TPA, might be offset by more rapid and effective revascularization achieved with the endovascular approach,” they wrote.

The SYNTHESIS Expansion study was sponsored by the Italian Medicines Agency. Dr. Ciccone said that he has served on the advisory board for Concentric Medical.

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