THURSDAY, May 28, 2009 (HealthDay News) -- A new analysis showing that a potent clot-dissolving drug can safely be used to treat strokes four-and-a-half hours after symptoms begin has prompted a change in a current recommendation, which set a three-hour deadline for the medication's use.
The review of 1,622 cases of people treated with tissue plasminogen activator (tPA) in four separate studies finds that the benefit in keeping brain cells alive outweighs the risk of brain-damaging bleeding when the drug is given up to 4.5 hours after first symptoms, according to a report in the May 28 online issue of Stroke. The most convincing results came from the latest study, in which 821 people were treated later than is currently recommended.
"By pooling data from four prior clinical trials in which patients were treated with tPA between three and four-and-a-half hours, we were able to demonstrate that treatment with tPA is beneficial even if it is started between three and four-and-a-half hours of symptom onset," said study author Dr. Maarten Lansberg, an assistant professor of neurology and neurological sciences at Stanford University.
An advisory committee of the American Stroke Association/American Heart Association (ASA/AHA) promptly issued a recommendation that the window for tPA therapy be opened that much wider; that advisory appears in the same issue of Stroke.
"The advisory updates the current guidelines to recommend treatment in select patients in the three- to four-and-a-half hour window, but urges confirmation of the trial's results with further analyses," according to a statement issued by the ASA/AHA.
"In practical terms, wide adoption of the recommendation would mean that 2 percent to 3 percent more people who suffer strokes caused by blockage of a brain artery would receive tPA therapy," said Dr. Jeffrey L. Saver, a professor of neurology at the University of California, Los Angeles, and a member of the advisory committee.
That might not seem a great leap forward, but Saver noted that "right now, at well-performing hospitals, 5 to 10 percent of stroke patients are treated in under three hours."
"That disappointing number is due primarily to the widespread failure of people to know the symptoms of a stroke and take immediate action when they are seen," he said.
"This re-emphasizes that what we need to highlight for the public is the importance of getting aid as soon as symptoms begin," Saver said. "Therapy with tPA is most effective when given in the first hour. One hour is better than two, two is better than three, three is better than four. Should there be weakness on one side of the body, trouble speaking, trouble with vision, if any of those signs occur, call 911 at once."
The chief concern with tPA is that it might cause excess bleeding that damages the brain, Saver said. But data cited in the new study show that "for every 100 patients treated with tPA between three and four-and-a-half hours after symptoms, 16 will have a better outcome, and two or three will have a worse outcome," he said. "The treatment has risks, but we help six patients for every one we harm."
The benefit is seen in the 80 percent to 85 percent of strokes caused by an artery blockage. Treatment with tPA is not recommended for the 10 percent to 15 percent of strokes that are caused by a burst brain vessel.
The U.S. Food and Drug Administration set a three-hour limit on use of tPA in strokes when it was approved 13 years ago, Saver noted. "Now we have the first expansion of guidelines for giving a clot-dissolving drug, so it is an important advance in stroke care," he said.
But tPA should not be used beyond the three-hour limit in a number of cases, the advisory committee said -- people aged 80 and older, those having a severe stroke, those with a history of stroke and diabetes and those taking clot-preventing drugs such as Coumadin.
For anyone who has a stroke, "time lost is brain lost," Saver said. "Every minute, 2 million neurons die. What we want to see is door to needle time of 60 minutes."
Stroke symptoms and what to do about them are described by the American Heart Association.