A hemophilia drug sharply cuts the chances that victims of the most devastating type of stroke will die or be severely disabled, providing the first possible treatment for brain hemorrhages, researchers reported yesterday.
An international study involving 400 patients found that a single infusion of the drug, a synthetic version of a naturally occurring protein, given within three hours after onset cut by about one-third the risk of death or severe disability among patients in the midst of a bleeding stroke. This type of stroke hits about 80,000 Americans each year and about 2 million people worldwide.
The findings mark only the second time that any treatment has been shown to be effective for any type of stroke and the first time a treatment has been found effective for bleeding strokes, which are the deadliest and most disabling.
"These results are beyond my wildest dreams," said Stephan A. Mayer, an associate professor of neurology and neurosurgery at Columbia University Medical Center in New York, who led the study. "I thought this might work, but I had no idea it would work so well. I'm walking around in a state of shock. I'm very excited."
Although the drug, NovoSeven, probably requires additional testing before winning formal approval for use with stroke patients, Mayer and other experts predicted it would likely become the standard treatment and transform care for what had essentially been tens of thousands of hopeless patients.
"The results we've seen are just so eye-popping that I have no doubt that eventually this is going to become the standard treatment for stroke around the world," said Mayer, who unveiled his findings at the World Stroke Congress in Vancouver. "The results are so clear, so consistent and so robust it is truly remarkable."
Other experts welcomed the findings.
"This is very significant. It's something that we've been looking for and hoping for and waiting for," said Larry Goldstein, director of the stroke center at the Duke University Medical Center who also serves as a spokesman for the American Stroke Association. "We've been in desperate need of new ways of trying to treat patients. It's very, very important."
The advance underscores the need to seek treatment quickly when people experience stroke symptoms, said Harold Adams, a professor of neurology at the University of Iowa. "This is another breakthrough for stroke care and will increase the importance of our efforts to emphasize early treatment of stroke," Adams said.
Some researchers, while praising the findings, cautioned that the drug carries risks. More testing was needed to gauge the relative risks and benefits, especially because the trial was not specifically designed to prove effectiveness, they said.
"We need a larger-scale trial to really prove whether this is beneficial," said Steven Warach of the National Institute of Neurological Disorders and Stroke. "But this is an extremely exciting finding. It's very encouraging."
About 700,000 Americans each year suffer strokes, the leading cause of disability in the United States and the third leading cause of death. Eighty percent of strokes occur when a blood clot blocks a vessel in the brain, killing brain tissue. In 1995, doctors developed the first effective way to stop this type of stroke -- injecting patients with the clot-dissolving drug tissue plasminogen activator, or tPA.
But about 15 percent of stroke victims suffer another type known as a hemorrhagic stroke, which occurs when small blood vessels in the brain burst. Those are the most deadly and most likely to leave survivors severely disabled, with one-third to one-half dying and most of the survivors being left severely disabled. There has never been an effective treatment.
"There has been nothing -- ever. It has the highest mortality and leads to the worst outcome of any kind of stroke. It's devastating," Mayer said. "The really horrible part is that when someone gets hits by one of these they get a headache, then they collapse. They get paralyzed and they sink in to coma. The only thing you can do is put someone on life-support."
Mayer proposed trying NovoSeven, which was developed to stop hemophilia patients from bleeding to death. The drug is a laboratory-produced version of a naturally occurring protein, called factor VIIa, that causes blood clots to form.
In the study, designed primarily to test the drug's safety and potential for reducing bleeding, patients received an intravenous infusion of either the drug, given in one of three different doses, or a placebo. A CAT scan 24 hours after receiving the treatment showed that any of the three doses reduced by about half the amount of bleeding in the brain, Mayer said.
But when the researchers followed the patients for three months, they found that those receiving the drug were approximately 30 percent less likely to die or be left severely disabled -- paralyzed or in a coma. About 70 percent of those who received the placebo either died or were left severely disabled, compared with about 50 percent of those receiving the drug, Mayer said.
"On average, for every six patients you treat, you are going to eliminate one death or severe devastation," he said.
Those receiving the drug were, however, about 6 percent more likely to suffer heart attacks or strokes caused by blood clots.
While Mayer said those increased risks were far outweighed by the benefits, Warach cautioned that it remains a key question that required a larger, follow-up study.
The study was funded by the drug's maker, Novo Nordisk of Denmark, but Mayer said he has no financial interest in the company or the drug.
"We are extremely encouraged by this trial data for NovoSeven, which confirms there is at last a proven safe treatment for this most deadly type of stroke," said Lars Rebien Sorensen, Novo Nordisk president and CEO.
The drug is expensive, costing about $7,000 per dose, but Mayer said the cost is easily offset by the savings in medical expenses of caring for severely disabled patients.
"For stroke physicians, this is huge," Mayer said. "There is now finally something that we can give patients."