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Neurology Today At the Meetings: International Stroke Conference

Access daily, concise peer-reviewed reports from the International Stroke Conference selected by the Neurology Today editors.

Wednesday, February 13, 2019

Safety Window for tPA Extended Up to 9 Hours for Ischemic Stroke

BY ED SUSMAN

HONOLULU—Stroke patients who have viable brain tissue can safely and effectively undergo tissue plasminogen activator (tPA) thrombolysis as long as nine hours after onset of stroke symptoms, researchers reported here at the 2019 International Stroke Conference, sponsored by the American Stroke Association.

In the study, 113 patients received thrombolysis and 112 patients were assigned to placebo. The patients receiving tPA were older, with a mean age of 74 compared to a mean age of 71.4 for placebo patients.

In the primary outcome measure, 37 percent of patients treated with tPA in the nine-hour window—including those with so-called "wake up" strokes—achieved a modified Rankin Scale (mRS) score of 0–1 at 90 days compared with 29 percent of patients who were treated with placebo in the Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) trial (p=0.045), said Henry Ma, MD, PhD, director of physician training at Monash University in Melbourne, Australia.

In the secondary outcome measure—achieving a mRS score of 0–2 at 90 days—the milestone was achieved by 51 percent of the patients treated with tPA compared with 43 percent of the patients on placebo therapy (p=0.022), Dr. Ma said in his late-breaker oral presentation.

"EXTEND is the first positive thrombolysis trial in an extended time window using automated penumbral imaging," he said. "The current guideline for thrombolysis in acute ischemic stroke is less than 4.5 hours from stroke onset. But advanced imaging studies from our group and others suggest that the ischemic penumbra can exist up to 24 hours after onset and its salvage can lead to improved outcome."

An automated algorithm uses computer assisted tomography scans to determine penumbral mismatch and to select likely candidates for tPA thrombolysis.

The EXTEND researchers reported, among other findings, that tPA resulted in 25 percent of patients achieving early neurological improvement based on an 8-point or better reduction on the National Institutes of Health Stroke Scale compared with 10 percent of placebo patients (p=0.002); 51 percent of patients achieving 90 percent reperfusion at 24 hours compared with 28 percent of placebo patients (p=0.001); 73 percent of patients achieving 50 percent reperfusion at 24 hours compared with 53 percent of placebo patients (p=0.009); and 70 percent of patients achieving recanalization at 24 hours compared with 40 percent of placebo patients (p<0.001).

Death at 90 days occurred in 9.5 percent of the placebo patients and in 10 percent of the tPA patients (p=0.94). Symptomatic intracranial hemorrhage occurred in 1.0 percent of the placebo patients and in 6 percent of the tPA patients (p=0.071).

"There was an increase in the rate of symptomatic intracranial hemorrhage consistent with other thrombolytic trials, but this was not associated with increased mortality and did not negate the positive results of the improved rate of excellent functional outcome," Dr. Ma said.

In commenting on the study, Joseph P. Broderick, MD, FAAN, professor of neurology at the University of Cincinnati, said: "It makes sense that anything that can open up the vessel among people who have at-risk brain and not dead brain could benefit these stroke patients. This study did meet its primary endpoint."

Dr. Broderick said the success of the thrombectomy studies made it necessary to end EXTEND before the full complement of 310 patients had been recruited because doctors were sending the EXTEND candidates to thrombectomy.

"I think these results will help us push the window out further for the use of thrombolytic drugs as long as it looks like you have patients with salvageable brain," he said. "In general, the longer you wait, the worse you get, but there are people who have enough collateral flow that gives us a longer time window to treat them. But you still want to treat as quickly as possible.

"We now should be thinking of a physiological clock rather than a chronological clock in assessing these stroke patients," Dr. Broderick suggested. "But you have to treat as soon as possible after you get that physiological picture because the clock keeps ticking."

Boehringer Ingelheim provided the study drug for the EXTEND trial and iSchemaView provided the RAPID software platform used for patient selection.

Dr. Ma had no disclosures.

LINK UP FOR RELATED INFORMATION:

ISC Abstract LB21: Ma H, Campbell B, Churilov L, et al. Extending the thrombolytic time window to 9 hours for acute ischemic stroke using perfusion imaging selection - The final result.