Stroke sufferers can still benefit from clot-busting medicine even if they receive it an hour or so beyond the current three-hour window after symptoms start, an important new study suggests.
The finding could potentially extend treatment to thousands more people each year and prevent many from being left disabled. However, it does not change long-standing advice that stroke victims seek immediate help if they feel sudden numbness or weakness in the face, arm or leg.
"Don't wait," said Dr. Larry Goldstein, director of Duke University's stroke center and a spokesman for the American Stroke Association. "If you think you are having symptoms, call 911."
The study by European doctors found that the clot dissolver could safely be given up to 4 1/2 hours after the start of symptoms. Results were published in Thursday's New England Journal of Medicine.
Stroke is the nation's No. 3 killer and the leading cause of disability such as paralysis or speech loss. More than 700,000 Americans suffer a new or recurrent stroke each year and more than 150,000 die. The most common strokes result from a blood clot blocking an artery supplying blood to the brain, starving brain cells of oxygen.
The best treatment is giving patients the drug TPA to break up the clot and open the artery. A large federal study in 1995 showed that people fared better when given the drug within three hours of the start of a stroke. Beyond that, studies have shown the drug can raise the risk of dangerous bleeding in the brain and may not be as effective.
However, only about a third of stroke victims seek help that fast, and fewer than 5 percent get TPA now. Some doctors have been trying to push the time limit, and the new study is the largest and most rigorous to test that approach.
Doctors randomly assigned 821 stroke patients in Europe who were not treated within three hours to receive an intravenous dose of TPA or a dummy drug up to 4 1/2 hours after symptoms started.
Doctors found those given TPA fared better — 52 percent survived without major disability compared with 45 percent of the others. The drug group had more cases of bleeding in the brain — 27 percent versus 18 percent. However, it was serious in only about 2 percent. The death rate was similar in both groups.
The study was funded by Boehringer Ingelheim Pharmaceuticals Inc., which markets TPA as Actilyse overseas. TPA is sold in North America by Genentech Inc. as Activase.
Last week, the same researchers reported similar results in a less rigorous observational study of 664 stroke patients also given TPA after three hours.
Dr. Lee Schwamm, director of Massachusetts General Hospital's acute stroke program, estimated that nearly 20,000 more patients a year could be treated under the time extension.
"I strongly believe it has the potential to have a major impact on practice" in the United States, said Schwamm, who had no role in the research.
Some experts worry that some patients and doctors may take their time treating strokes given the extra window.
"It is very clear that our focus must remain on the door-to-needle time. Every minute matters during a stroke," Dr. Patrick Lyden, head of the University of California, San Diego stroke center, wrote in an accompanying editorial.
Stroke neurologist Dr. Walter Koroshetz of the National Institutes of Health said treatment guidelines deserve a fresh look "to try to break this three-hour barrier."
Koroshetz said it's not clear which patients might benefit most from the extra time. Since the European study focused on mild stroke cases, it's unknown if severe stroke victims would also benefit, he said.
Dr. Kenneth Gaines, stroke director at New Orlean's Ochsner Medical Center, said he might be more willing to consider giving TPA in borderline cases. But he remained concerned about the bleeding side effects.
"The real solution is to move faster," Gaines said. "There is diminishing return the longer you delay treatment."