Long-awaited stroke studies show hopeful new treatment no better than older one

istockphoto - Three new studies have shown that a new approach to treating strokes is not as useful as was once thought.

Early observations suggested that approaching the clot with a catheter and either injecting clot-dissolving drugs into it or snagging it and pulling it out produced better results. In 2004, the FDA began approving use of the catheters in the brain because they had been proved useful elsewhere in the body. The three studies reported this week (which will eventually be published in the New England Journal of Medicine) tested the hypothesis in a rigorous way.

In the largest trial, called IMS III, all patients got the IV clot-dissolving drug tPA within three hours of the start of stroke symptoms. Half were then assigned to get an imaging study that looked at the arteries of the brain to see whether a blockage remained. If it did, the doctors went after it with an endovascular procedure. The other half of the patients got standard treatment, which didn’t include the procedure. Forty-one percent of patients recovered completely in the endovascular group and 39 percent recovered completely in the control group, outcomes that were no different statistically. Death within three months was essentially the same too: 19 percent vs. 22 percent.

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In the Italian study, called SYNTHESIS Expansion, 362 stroke patients were randomly assigned to get either IV tPA or endovascular treatment. At three months, 35 percent of the patients in the tPA group were alive without any disabilities, compared with 30 percent of the endovascular group. That also was not significantly different.

The third study, called MR RESCUE, run out of Georgetown University, was more complicated.

It randomly assigned 118 patients less than eight hours out from the start of their strokes to receive standard care or have the clot removed with a catheter device. They also got CAT or MRI scans to see whether they had a large or small amount of brain tissue still alive and salvageable. Removing the clot wasn’t better than standard care in either group — those with a lot or a little brain tissue to lose.

“I think everybody was a little surprised. But mainly disappointed,” said Chelsea S. Kidwell, the Georgetown neurologist who headed the study.

Why endovascular treatment wasn’t better is a mystery that the researchers are struggling to explain. The answer could be in the patients, the device or the timing of the procedure.

In IMS III, patients with large strokes benefited from clot removal more than those with small ones, but there weren’t enough patients in the study to make such a fine distinction with certainty.

“It’s a hint. But it’s not proof,” Broderick said.

In MR RESCUE, only 67 percent of arteries opened up completely after the clot was grabbed. Current devices, which use a mesh stent to hold the clot more firmly, are successful more than 80 percent of the time.

“The stroke community is hopeful that with the new generation devices we will show better outcomes,” Kidwell said.

In the Italian study, patients getting endovascular treatment were 3.75 hours into their stroke — an hour longer than those getting IV treatment, because of the logistics of assembling the procedure team. “That hour could have made a difference. We know that ‘time is brain,’ ” Ciccone said.

The three trials demonstrated how hard it is to test things once they’re in widespread use. History is replete with treatments (such as supplemental oxygen for premature infants) and devices (such as pulmonary artery catheters) used routinely before being shown to be harmful or of little value.

It took from 2004 to 2011 for the MR RESCUE team to recruit the 118 patients in the trial. It had permission to run the study in 30 hospitals but found only 22 that were willing to participate. More than 10 other hospitals were invited to join but declined because their neurologists were already convinced the catheter treatment was better — a view that turns out not to be true.

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