Window of opportunity for stroke treatment widens

Use of clot-busting drugs as long as 4 ½ hours after an event pays dividends later

Normal 0 false false false MicrosoftInternetExplorer4 Emergency room physicians can deliver clot-busting treatments to a wider range of stroke patients than previously thought, European researchers report in the Sept. 25 New England Journal of Medicine.

The finding could change the way stroke is treated and increase ER doctors’ ability to prevent some cases of disability caused by strokes, scientists say.

Most strokes result when a blood clot lodges in the brain, blocking blood flow to other parts of the organ. A powerful drug called tPA, or tissue plasminogen activator, can dissolve these clots. But medical dogma holds that it must be given within three hours of a stroke’s onset. Beyond that, the thinking goes, the bulk of the brain damage is done and adding the risk of internal bleeding that accompanies clot-busters seems unwise. The new study extends that window of effective tPA treatment by 90 minutes, to 4 ½ hours.

This precious extra time to dissolve a clot and restore blood flow to a starving portion of brain could benefit tens of thousands of stroke patients in the United States each year, says study coauthor Werner Hacke, a neurologist at the University of Heidelberg in Germany.

“I think this is big news because suddenly they have substantially extended the number of patients who get intravenous tPA,” says Scott Kasner, a neurologist at the University of Pennsylvania in Philadelphia.

However, many emergency room physicians are hesitant to give stroke patients clot-busting drugs at all. A landmark 1995 study found that giving the drugs within three hours of stroke onset provided benefits that outweighed the bleeding risk in most patients. But only about 4 percent of stroke patients who arrive at U.S. hospitals get tPA, says neurologist Patrick Lyden of the VeteransAffairsSan DiegoMedicalCenter and University of California, San Diego, who coauthored the 1995 report. Most stroke patients don’t receive tPA because the time of onset might be hazy, or doctors may be hesitant to risk incurring bleeding or are untrained in delivering tPA. The new data should clarify the time frame and allay some doubts about the treatment’s effectiveness, he says.

In the new study, Hacke and his colleagues identified patients who arrived at hospitals with a stroke that had begun more than three hours but less than 4 ½ hours earlier. The researchers used CT scans of the brain to rule out people with brain bleeding. The doctors also excluded those with severe strokes as indicated by the scans.

That left 730 patients, half of whom were then randomly assigned to get infusions of the tPA drug called alteplase. The others received a placebo.

After three months, roughly 52 percent of study patients treated with tPA within the extra 90 minute time window had normal daily function and were living independently, compared with 45 percent of those getting a placebo infusion. The death rate over three months was about 8 percent in both groups.

Doctors detected brain bleeding among treated patients about as often as seen in previous studies in which tPA was limited to a three hour window.

Time matters in stroke treatment, and delay is dangerous. As minutes or hours pass with a clot lodged in place, more brain tissue is starved of blood and damaged. Thus, busting a clot later into the stroke might rescue less tissue. “The [beneficial] effect of tPA decreases over time,” Hacke says.

Even so, treated patients in this study — who received tPA an average of four hours after the onset of stroke — still showed clear benefits over the placebo group.

“I think this will eventually be incorporated into clinical practice, slowly at first, and then become the standard of care,” Kasner says.

Stroke disables more adults than any other condition, yet every stroke is different. People who have a severe stroke are often rushed to a hospital with obvious problems, Hacke says. But those with milder strokes sometimes show up longer after a stroke’s onset, in part because they aren’t sure whether their symptoms are serious enough for a hospital visit, he says. These are the kinds of people most likely to benefit from the new study’s findings on delayed tPA treatment, he says.

Meanwhile, Lyden says, more hospitals need to grasp the value of tPA and have doctors on site or on call who can deliver it. “Every hospital needs to have a stroke plan,” he says. “Either have a way to give tPA, or set up a way to tell the EMS people to divert [an ambulance] to a place that can do it.”

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