PITTSBURGH _ When a stroke occurs, a harsh deadline looms. The quicker the clot is removed from the major blood vessel in the brain, the more brain function is salvaged.
For that reason, when it comes to ischemic strokes, the medical mantra is "time is brain," with the current guidelines saying treatment should occur within six hours.
Now, the randomized clinical DAWN study involving the University of Pittsburgh Medical Center, or UPMC, and presented Tuesday during the European Stroke Organization Conference 2017 in Prague, argues against a time limit for treatment by showing that a brain scan can determine well after the six-hour deadline whether endovascular treatment can save brain function and limit disability.
The procedure involves inserting a micro-catheter into the affected blood vessel, using a stent to expand it then removing the clot. Earlier always is better, but benefits actually can occur six to 24 hours after the stroke _ and even longer.
The study is being called a "game-changer" by the past president of the American Heart Association.
"This still means that you need to be rushed to the hospital as soon as possible after a stroke has occurred because the mantra _ 'time is brain' _ still holds. However, our study shows that even if treated outside the time window, patients will have significantly reduced disability with clot removal," said trial co-author Tudor Jovin, director of the UPMC Stroke Institute and University of Pittsburgh professor of neurology and neurosurgery.
Key is the "clinical core mismatch" _ a smaller portion of permanent damage in the area of the brain served by the clogged vessel, as compared with a larger area or "penumbra" that's under immediate threat but still is alive.
The study found that beyond the six-hour deadline, about one-third of the patients who qualified for the treatment still showed enough of a mismatch to merit the endovascular procedure.
Study results show why: About 49 percent of the patients in the study who received endovascular therapy after the standard deadline were shown to have independent levels of functioning 90 days after treatment, compared with only 13 percent in the control group. There were no differences in mortality levels between the two groups.
"You can salvage the penumbra, bring back the brain and prevent if from dying," said Dr. Jovin, in a phone interview from Prague. "So you end up with a small area of damage rather than a larger area of permanent damage, regardless of the point in time when the stroke occurred." If the scan shows potential, the procedure should be done.
When a person arrives at the hospital, many receive a clot-busting drug _ tissue plasminogen activator or tPA _ that works to dissolve the clot but isn't always effective. Drug treatment typically ends 4{ hours after the stroke occurred, with use of aspirin and therapy used from the six-hour point on, Dr. Jovin said.
In the study, researchers randomly assigned stroke victims who arrived in the hospital outside of the six-hour time window to receive either endovascular therapy or the standard medical therapy, a UPMC release states. Brain imaging and clinical information measuring the level of neurological deficit were used to identify and enroll patients who had a mismatch _ a small area of irreversibly damaged brain vs. a significantly larger area of brain tissue area still alive.
There were plans to enroll 500 patients for the study. But an intermediate review of the endovascular treatment's effectiveness before enrollment was completed led the independent Data Safety Monitoring Board overseeing the study to recommend early termination of the trial based on demonstrated clinical benefits that the endovascular treatment had on selected patients.
Ralph Sacco, past president of the American Heart Association and chairman of neurology at the University of Miami Miller School of Medicine, said the association will await results from a similar study led by the National Institutes of Health before making changes in treatment guidelines.
"This (DAWN) study is really exciting news because of the overwhelming, strong, positive findings; the strong safety of the procedure; and because this really opens up opportunity to treat more patients with stroke due to the larger time window, and it also addresses wake-up strokes _ those that occurred while the person was sleeping," he said. Such patients typically have gone beyond the six-hour treatment window, with 65 percent of the patients in the study having had wake-up strokes.
"I think this will be a game-changing study, and of course, we will await results from NIH study," Dr. Sacco said. "But it is pretty impressive."
