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For the second time in as many days, researchers' expectations that endovascular therapy would improve outcomes in patients with acute ischemic stroke have been dashed.

Compared with intravenous thrombolytic therapy alone, giving endovascular therapy after thrombolytic therapy did not improve outcomes in patients with acute ischemic stroke, the Interventional Management of Stroke (IMS) III investigators reported online in the New England Journal of Medicine and at the International Stroke Conference in Honolulu.

On Wednesday, Italian researchers reported results of a head-to-head trial showing that endovascular therapy did not improve outcomes compared with IV tPA. That study also was reported in NEJM and at the meeting.

IMS III was stopped early, after 656 participants had been randomized, because the proportion of patients with functional independence at 90 days did not differ significantly according to treatment: 40.8% with endovascular therapy versus 38.7% with IV tPA.

After adjustment for National Institutes of Health Stroke Scale (NIHSS) strata, that's an absolute difference of just 1.5 percentage points (95% CI -6.1 to 9.1), according to Joseph P. Broderick, MD, of the University of Cincinnati Neuroscience Institute, and colleagues.

On the flip side, endovascular therapy did not appear to cause any harm, with similar safety outcomes in both groups, Broderick told 麻豆传媒.

Broderick said that he and his team expected the combination approach to improve outcomes by at least 10 percentage points. That's because the one-two punch combines the advantages of a rapid start with IV tPA with a means of eliminating large clots that persist after treatment.

Also, studies suggest endovascular therapy is associated with nearly twice the rate of recanalization of the affected cerebral artery. But researchers are increasingly learning – from this trial and others -- the limitations of revascularization as a surrogate measure for efficacy, he said.

In IMS III, patients ages 18 to 82 who received IV tPA within 3 hours of symptom onset were randomized in a 2:1 fashion to receive additional endovascular therapy or not. Those in the endovascular group underwent angiography as quickly as possible, and those with no evidence of a treatable occlusion received no additional treatment.

Those with a treatable occlusion received endovascular therapy with intra-arterial tPA or mechanical clot disruption or retrieval, at the choice of the neurointerventionalist. Angiography had to begin within 5 hours and be completed within 7 hours of symptom onset.

At the time the trial was stopped, there were 434 patients in the endovascular arm and 222 in the IV tPA arm.

The primary outcome measure was functional independence, defined as a score of 2 or less on the 6-point modified Rankin scale in which higher scores indicate greater disability.

There were no significant differences in rates of functional independence in any of the predefined subgroups of patients, including those with an NIHSS score of 20 or higher and those with a score of 19 or lower.

In addition, there were no differences in mortality at 90 days (19.1% in the endovascular group versus 21.6% in the IV tPA group, P=0.52) or symptomatic intracranial hemorrhage within 30 hours of initiation of tPA (6.2% and 5.9%, respectively, P=0.83).

However, there was a "trend toward benefit" in patients with more severe strokes (NIHSS scores of 20 or more), in patients with clots in the terminal part of the internal carotid artery, and in patients treated more quickly, Broderick said. He believes future randomized trials should focus on such patients.

The time to intra-arterial treatment was 32 minutes longer in IMS III compared with the two pilot studies that preceded it. This may help to explain the lack of clinical benefit despite substantially better revascularization with intra-arterial therapy. "We probably did not open the arteries quickly enough," said Broderick.

American Stroke Association spokesperson Ralph Sacco, MD, head of neurology at the University of Miami, said he was disappointed by the results. "We have all had cases where we saw recanalization with endovascular approaches and then saw recovery. We were hoping for this to be borne out in the trial," he said.

Sacco told 麻豆传媒 that endovascular technology is "always improving. Perhaps the use of more modern stent retrievers, which were used in only a small number of patients in this trial before it was halted, would provide greater benefit," he said.

From the American Heart Association:

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