After three decades of failure, researchers have found a treatment that greatly improves the prognosis for people having the most severe and disabling strokes. By directly removing large blood clots blocking blood vessels in the brain, they can save brain tissue that would have otherwise died, enabling many to return to an independent life.
The study, published online Wednesday in The New England Journal of Medicine and conducted by researchers in the Netherlands, is being met with an outpouring of excitement. One reason the treatment worked, researchers suspect, is that doctors used a new type of snare to grab the clots. It is a stent, basically a small wire cage, on the end of a catheter that is inserted in the groin and threaded through a vein to the brain. When the tip of the catheter reaches the clot, the stent is opened and pushed into the clot. It snags the clot allowing the doctor to withdraw the catheter and pull out the stent with the clot attached.
"This is a game changer," said Dr. Ralph L. Sacco, chairman of neurology at the University of Miami's Miller School of Medicine. "A sea change," said Dr. Joseph Broderick, director of the neuroscience institute at the University of Cincinnati.
About 630,000 Americans each year have strokes caused by clots blocking blood vessels in the brain. In about a third to half, the clot is in a large vessel, which has potentially devastating consequences. People with smaller clots are helped by the lifesaving drug tPA, which dissolves them. But for those with big clots, tPA often does not help. Until now, no other treatments had been shown to work.
The new study involved 500 stroke patients. Ninety percent got tPA. Half were randomly assigned to get a second treatment, as well. A doctor would try to directly remove the clot from the patient's brain. The study did not specify how the removal would happen. There are several methods, but the vast majority were treated with the new stent.
One in five patients who had tPA alone recovered enough to return to living independently. But 1 in 3 who also had their clot removed directly were able to take care of themselves after their stroke. And that, said Dr. Larry B. Goldstein, director of the Duke Stroke Center, is "a significant and meaningful improvement in what people are able to do."
It has been a long road to this success, explained Dr. Walter J. Koroshetz, acting director of the National Institute of Neurological Disorders and Stroke. It began in the 1980s when researchers began testing intravenous tPA. It dissolved small clots and saved many patients' brains but was not as effective in dissolving the big clots that are truly devastating. In 1995, when the first large study was published demonstrating tPA's effectiveness, stroke experts were jubilant. They were left, though, with the problem of helping people with large clots.
Companies began marketing various clot-snaring devices, but there were no studies showing they helped. Using them could be risky - some involved pushing wires through twisting blood vessels that often were damaged already from atherosclerosis, Koroshetz explained. "You could puncture an artery and if you do and get bleeding in the brain, you have a problem," he said. Another problem was that sometimes fragments of a clot could break off and be swept deeper into the brain, causing new strokes.
The systems were also expensive. Giving a patient tPA cost about $11,100. Using one of the new devices could cost $23,000, Koroshetz said.
But some neurologists were enthusiastic. The Food and Drug Administration cleared the first device for clot removal in 2004, allowing it to be marketed. The clearance was granted because the agency considered the device to be equivalent to something already in use - devices used to snare pieces of wires or catheters that might break off in a blood vessel during a medical procedure.
That, other neurologists said, was not at all the same as going into the brain to grab a clot. "There was a lot of controversy," Koroshetz said. But the devices quickly came into widespread use. It took time and experience for doctors to learn to use the devices, and not everyone had the necessary expertise.
Even so, said Dr. Diederik Dippel, professor of neurology at Erasmus University Medical Center and principal investigator for the new study, when his study was about to begin people questioned why it was even needed. "People said why bother with a clinical trial. Just do it," Dippel said.
The study began in 2010. In the meantime, several other large clinical trials testing clot removal were well underway, including one sponsored by the National Institute of Neurological Disorders and Stroke and headed by Broderick. By 2012, with 650 out of the planned 1,000 patients enrolled, the study was ended. "Because of futility," Koroshetz said. It had become clear that, if anything, those randomized to have their clots directly removed were doing no better.
Two other clinical trials also ended without showing benefit. All too often, attempts to remove clots resulted in uncontrolled bleeding in the brain. Gloom settled over the field. In the Netherlands, Dippel said, attitudes about the trial reversed. "Everyone said, 'Why should we go on?'" Dippel said.
But the Dutch study happened to start at a time when there were a few key developments that made it possible to hope for success. There was new technology that allowed doctors to quickly assess whether a stroke patient had a large clot and, if so, where it was. In previous studies they tried to guess from a patient's symptoms. And the stent system for snagging a clot seemed safer and easier to use than previous devices.
The stent system, said Dippel, "was clearly a better device than we were used to."
Of course, said Goldstein, he would like to see the results confirmed with other studies. But, he and others say, that may already have happened. Two other studies like the Dutch one were just ended early because the results were so positive. The data will be presented in February at the International Stroke Conference in Nashville, Tennessee.
Now neurologists are increasingly confident that, at last, they have something in addition to tPA to offer patients. "I think this is the real thing," Koroshetz said.
© 2014 New York Times News Service