A Baltimore cardiologist says a major international study that found that three clot-dissolving drugs work equally well to reduce the death rate of heart attack victims may be premature.
hTC Another study, which already has begun and also will involve about 45,000 patients worldwide, now is being touted as the one "that will once and for all settle" the long-debated question of which drug is most effective, Dr. Raymond Barr said yesterday.
Barr, who provided research on 90 patients in the Third International Study of Infarct Survival (ISIS), was at the American College of Cardiology meeting in Atlanta last weekend where the results were announced and the new study was disclosed.
"I just want people to know that it may be premature to jump from these initial results of the ISIS study," said Barr, medical director of the Paul Dudley White Coronary Care Center at St. Agnes Hospital.
The drugs examined in the ISIS study were tPA, or alteplase, and APSAC, or anistreplase, the newest and most costly clot-busters; and streptokinase, sold under the brand name Streptase, which is 30 years old and the cheapest.
All three drugs work by dissolving clots that cause heart attacks and limiting damage to the heart muscle. They are most effective when used within four to six hours after a heart attack but can save lives if given any time in the first 24 hours.
The new investigation, known as the Global Utilization of Streptokinase and tPA on Occluded Vessels, or the GUSTO study, will be centered at Duke University and the University of Michigan, said Barr. He plans to enroll 90 patients.
The study will look at the use of tPA, a genetically engineered human protein which dissolves the clot that blocks a coronary vessel when it is combined with an intravenous injection of heparin. In addition, it will examine streptokinase alone and a combination of tPA, heparin and streptokinase.
Some smaller studies, reported in the past few months in the New England Journal of Medicine, have shown that intravenous heparin injections into the bloodstream can keep open heart vessels that shut down again in a significant number of patients who get tPA by itself, Barr said.
This information, however, was not available when the ISIS study of patients from more than 1,000 hospitals in 20 countries was started about two years ago.
"Some studies have shown that a combination of these agents -- tPA, heparin and streptokinase -- is much better than one drug alone," Barr also said. "Perhaps if we used tPA, heparin and streptokinase, we could reduce the mortality rate from 10 percent to 5 percent, improve on safety and, at the same time, reduce the price of treatment because we'd only be using half of the tPA."
Approved in 1987, tPA is the most widely used clot-busting drug in the United States and the most expensive, costing $2,200 for a course of treatment. The standard treatment for APSAC, approved in 1989, costs $1,700 while streptokinase costs $150 a treatment.
The ISIS study found the overall death rate from heart attack among patients in the study was 10 percent, with no significant difference seen among the three drugs.
Patients who received streptokinase had a lower frequency of brain hemorrhages, a type of stroke that can cause muscle weaknesses and other disabilities, than patients in either the tPA or the APSAC groups.
About 1.5 million Americans have heart attacks each year. Between 400,000 and 600,000 of them would be considered candidates for clot-dissolving drug treatment, but only about 20 percent actually receive the treatment in time for it to be effective.
Some experts believe this may be due, in part, to confusion about the drugs among doctors who treat heart attack patients. But others, like Barr, put the blame on patients themselves, "who are too busy on the treadmills of their lives" to take time to check out chest pains, often the early sign of a heart attack. Unless the clot is dislodged within four hours or so, part of the heart dies.
"People are taught from childhood up to 'tough it out,' " Barr said. "What happens is that time is like a river without banks. It just gets away from you and the next thing you know you have a total blockage of an artery and you're coming in crashing."