The costly clot-busting drug t-PA could prevent irreversible brain damage in some stroke victims, but only if it is delivered within a few hours of the onset of stroke.
Soon after, the window of opportunity slams shut. In fact, at that point, the drug is more likely to trigger deadly bleeding.
Healthcare systems and hospitals are just beginning to wrestle with the implications of this discovery.
The upfront cost of treating stroke is now much greater with the addition of the $2,250 per-dose drug. Emergency rooms must accelerate their treatment of stroke patients because minutes will be precious. And the public must be taught to identify stroke and act quickly, now that there is hope.
Experts urge caution in adopting the new therapy, because even though it's the first treatment proven effective for strokes, t-PA can be dangerous.
"There is a host of issues that require in-house education," warned Richard Koller, M.D., chairman of the stroke services program at 607-bed Abbott Northwestern Hospital in Minneapolis, which participated in a federally sponsored study of the drug.
"The (computed tomography) scan has to be very, very critically evaluated, as people who have early signs of stroke are more likely to bleed," Koller said. "There is a matter of blood pressure control. There is a list of criteria patients have to meet. If you can't identify the time frame of the stroke, patients shouldn't be treated."
Tissue plasminogen activator, or t-PA, is used commonly to treat heart-attack patients. But the federal study showed it also can be used to dissolve blood clots in strokes, restoring blood flow to the brain. The drug is manufactured by Genentech of South San Francisco, Calif.
In the study, t-PA significantly increased patients' odds of escaping strokes without permanent disability. Some 31% of patients given t-PA within three hours of the start of their strokes showed minimal or no disability three months later. Only 20% of patients in the control group did as well. The difference in death rates wasn't significant.
The study was sponsored by the National Institute of Neurological Disorders and Stroke. Results appeared in the Dec. 14, 1995, issue of the New England Journal of Medicine.
A second study, which examines the effectiveness of t-PA up to five hours after the onset of stroke, is expected to be completed in January 1997.
Until then, physicians must not risk using t-PA if more than three hours have elapsed. "The longer you wait, the more likely there is permanent damage to brain cells, and when you resupply blood, the more likely the vessels will rupture," Koller said.
Even within three hours, t-PA is a risky therapy. In the study, 6.4% of patients who were administered the drug suffered intracerebral hemorrhages, and more than half of those died.
"The data is very good, so there is no question we're going to cover (the treatment)," said Lee Newcomer, M.D., chief medical officer of United HealthCare Corp., a Minneapolis-based HMO. "The key is going to be getting emergency rooms real efficient. By the time the patient gets discovered, gets in the emergency room, gets triaged, 60 minutes to 90 minutes are already gone-and then you've got to get over to the CT scan."
Stroke is the leading cause of long-term disability in the nation and the third-leading cause of death.
Potentially, t-PA could be put to work in 440,000 stroke cases annually, or about 85%. The remaining strokes are caused by hemorrhages, not blood clots, so t-PA would only do harm. CT brain scans can be used to distinguish the two types.
Researchers also are examining the potential benefits of heparin, a cheaper drug that prevents new blood clots, although it doesn't attack existing clots. The use of streptokinase, a competing clot-busting drug one-tenth the price of
t-PA, hasn't been studied. The drug is more likely to cause bleeding than t-PA, physicians said.
The benefits of keeping stroke patients out of nursing homes should outweigh the cost of t-PA. But hospitals could find the new therapy a money-loser, at least initially.
A dose of t-PA represents about 25% of Medicare payment for stroke, said Thomas Royer, M.D., senior vice president for medical affairs at Henry Ford Health System in Detroit. Its flagship, 903-bed Henry Ford Hospital, was part of the federal study.
The drug increases hospital costs in other ways, too. Stroke patients treated with t-PA at Henry Ford Hospital stayed an average of almost 2.5 days longer than patients in the control group, for a total of 15.2 days.
The health system still is gathering data to compare the total costs of t-PA treatment with the costs of traditional treatment, including nursing home care and disability.
Several factors will determine whether other Henry Ford hospitals also offer the treatment or continue transferring patients to the flagship, Royer said. Patient volume is one key because it will help determine how well personnel provide the treatment and at what cost, he said.
"It would be great to have 400 or 500 (patients a year), so we're always ready to do it, seven days a week, 24 hours a day," Royer said.
Strokes now must be handled as treatable emergencies instead of as irreversible disasters, as they were in the past, said Steven Levine, M.D., director of the clinical stroke service at Henry Ford Hospital.
Emergency rooms should "go through each process-assessment, evaluation, triage," he advised. "See where time can be shaved. Assess patients with a CT scan immediately. Get blood work and IVs immediately. Run through the abilities of the various city emergency services. Your thinking is, `every minute counts.'*"
The biggest problem, however, is more than half of stroke victims don't arrive at emergency rooms even within 12 hours of the onset of stroke, Levine said. Family and emergency personnel often have been slow to act because, until now, little could be done to help stroke victims.
In the federal study, only about 5% of stroke victims turned out to be eligible for t-PA treatment. "The most common reasons people didn't get treated is because they came to the emergency room too late or we didn't know the exact onset of stroke," Levine said.
"If everybody knew as much about the warning signs and risk factors for stroke as they do about Joe Camel, we would be in good shape," he said. "The issue is, where does the money come from-the millions of dollars that are going to be needed to educate people in an effective way nationally that stroke is a 911 emergency. You can waste a lot of money making hospitals fast if you don't get people coming in."