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Clot Dissolver Doesn't Boost Survival in Cardiac Arrest Patients

WEDNESDAY Dec. 17, 2008 -- German doctors thought that giving the clot-dissolving drug tenecteplase (TKNase) to people with sudden cardiac arrest would improve survival.

Unfortunately, the drug, a form of tissue plasminogen activator (tPA), didn't work as hoped in a trial, but they haven't given up on the idea.

"In specific situations, those patients with pulmonary embolism, use of this thrombolytic agent can stabilize the patient and help the patient survive," said Dr. Bernd W. Böttiger, professor and head of the department of anesthesiology and emergency care medicine at the University of Cologne and lead author of a report in the Dec. 18 issue of the New England Journal of Medicine.

But pulmonary embolism, a blood clot that blocks a heart artery, is the underlying cause of sudden cardiac arrest only 5 percent to 7 percent of the time, Böttiger said. There was a small improvement in survival, though not great enough to be statistically significant, among people with pulmonary embolism in the trial he led, but there was no overall increase in the survival rate.

The trial, done at several European medical centers, was stopped after 443 people were treated for sudden cardiac arrest "because of low survival," the report said. It was started again with a change in the treatment routine but "terminated prematurely for futility after enrolling a total of 1,050 patients."

The 30-day survival rate was actually lower for people given tenecteplase: 14.7 percent versus 17 percent for those getting conventional treatment for cardiac arrest.

Better emergency treatments are desired because, Böttiger said, "in the U.S. and Europe every year, about 400,000 patients are suffering cardiac arrest, and only 5 to 10 percent will survive." The hope was that tenecteplase would dissolve artery-blocking clots that caused the hearts to stop, but it proved to be ineffective in the vast majority of patients -- those whose cardiac arrest was due to blockage of a major heart artery.

Failure to improve the overall survival rate was "a result that was not expected," Böttiger said. Although 17 percent of the people given standard emergency treatment in the trial survived, he attributed that the higher-than-average rate to the quality of care at the centers that participated in the study, describing it as "something that you can reach in such excellent emergency case systems, but only there."

Now the researchers are devising possible new trials with variations on the theme. "We haven't used thrombolysis [clot-busting] in combination with an anticoagulant," a drug that prevents formation of clots, Böttiger mused. "We could try heparin or other anticoagulants," he said. "We have several ideas and are working out different plans. I am absolutely convinced that it will result in a successful method. This is supported by a huge amount of animal studies, but the next step has not been decided."

Meanwhile, Böttiger said, administration of tenecteplase for someone who has sudden cardiac arrest "should be considered where pulmonary embolism is the suspected cause of the arrest."

Dr. Richard Pomerantz, clinical chief of cardiology at the University of Rochester in New York, said that giving a clot-busting drug such as tenecteplase when cardiac arrest is caused by a lung clot seems reasonable "because the heart itself is not in bad shape." But he said he is skeptical about its value when a heart artery blockage is the cause.

"First, there is small likelihood of being able to get the clot-dissolving medication to the area where it is needed because there is relatively low blood pressure," Pomerantz said. "Then, it takes awhile for it to work. It isn't a magic thing that opens the clot at once. It can take an hour or more for it to work."

"Thirdly, even if you open the artery, if someone has been without circulation for awhile, it's not only a question of getting it to restart but also to pump in an efficient manner," he said. "Often, what little effect you might produce is not enough to alter the outcome."

More information

To learn more about the why and how of tPa use, visit the American Heart Association.

Posted: December 2008


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