Stroke Drug Still Meets Resistance From Doctors Wary Of Its Risks

But the majority of the doctors surveyed said that if they had appropriate backup from neurologists and a brain scanner available to help them diagnose and treat appropriate patients, they'd give the drug, called tPA. And if the risk of bleeding associated with tPA could be reduced, more physicians said they'd use it.

The findings are from a newly published survey of 1,105 emergency physicians conducted by University of Michigan Stroke Program researchers and published early online in the Annals of Emergency Medicine. The authors say it shows there's still controversy over the use of tPA, or tissue plasminogen activator -- and a long way to go to improve access to the therapy.

The authors also emphasize that safe and appropriate use of tPA should involve team-based approaches, where neurologists, radiologists and other specialists work with emergency physicians to diagnose stroke and choose the best treatment.

In fact, the authors predict that tPA use will increase as hospitals increasingly form stroke teams and write plans for what to do when a stroke patient comes through the emergency department door. Primary Stroke Centers are now recognized by the main hospital accreditation organization, JCAHO; U-M is one of the nation's 113 centers certified so far.

"This survey shows that there's still major resistance to tPA use in the emergency medicine community, but we shouldn't blame ED physicians or ask them to handle this decision alone," says lead author Devin Brown, M.D., a U-M stroke neurologist. "Only through team decision-making will we be able to change current practice and improve acute stroke care delivery."

Used within the first three hours of a stroke's onset, tPA can break up the blood clots that cause 80 percent of all strokes (known as ischemic). This can restore blood flow in the brain, and reduce or prevent the risk of permanent damage. But tPA also carries a 1-in-15 risk of causing intracranial hemorrhage (bleeding) that can be fatal. Nearly 10 years after its approval by the FDA, tPA is still only used in about 10 percent of patients eligible to receive it, and in about 2 percent of all stroke patients.

Emergency stroke care should be more like trauma care, says study co-author and U-M Emergency Medicine chair William Barsan, M.D. He notes, "Not every hospital is a trauma center, but every hospital knows what to do when a trauma patient arrives -- and that response may entail treatment or transfer."

"If a hospital is going to treat strokes, it should have the specialists and standard protocols in place to make the care the best it can be, including appropriate tPA use," he continues. "But if a hospital can't make that commitment, it should transfer stroke patients or make it known to EMS agencies that stroke patients should be directed elsewhere." Barsan treated the first patient ever to receive tPA, during a clinical trial while he was at the University of Cincinnati in the early 1980s. He also co-chaired a National Institutes of Health consensus conference on acute stroke treatment.

Stroke is the third most common cause of death in the United States, and the leading cause of disability. More than 700,000 Americans suffer strokes each year, and about 170,000 of them die.

The survey is the first and largest of its kind. It was sent to 2,600 randomly selected members of the American College of Emergency Physicians, and asked doctors how likely they'd be to use tPA in an ideal patient if they had access to a computed tomography (CT) machine and specialists to consult with. CT scans can show immediately whether a stroke is caused by a clot or by a bleeding blood vessel; tPA can kill if given to patients with bleeding strokes.

The survey also asked them what would be the maximum risk of intracranial hemorrhage they'd tolerate from tPA, and what would be the lowest acceptable improvement in patients' neurological state that would convince them tPA was beneficial enough to warrant the bleeding risk. The authors performed cross-analyses of answers according to physician age, gender, training background, year of medical school graduation and type of hospital and population center.

In all, 40 percent of the physicians said it was very unlikely, unlikely or uncertain that they would give tPA to an ideal patient in an ideal setting. Thirty-six percent said it was likely they would give the drug, and the remaining 24 percent said they were very likely to give it.

When asked why they wouldn't give tPA, 65 percent of the reluctant or resistant physicians cited the concern over hemorrhage, 23 percent said they didn't perceive that the drug would provide benefit, and 12 percent gave both reasons.

In all, the physicians set an average upper limit of 3.4 percent intracranial hemorrhage risk as acceptable, and an average lower limit of neurological improvement of 40 percent. Those who were unlikely to use tPA set the bar higher: They wanted a maximum bleeding risk of 2.1 percent and a benefit of 45 percent relative improvement. Currently, research shows tPA bleeding risk to be about 6.4 percent, and its benefit to range from a 30 percent to 50 percent greater chance of complete or almost-complete recovery. Bleeding risk from clot-busting therapy for heart attack is 1 percent.

There was no significant difference among doctors in urban, rural and suburban settings, or teaching and non-teaching hospitals. Women doctors were twice as likely as men to be willing to use tPA.

Interestingly, 30 percent of all the physicians said that their own personal experience with tPA had influenced their answers on the survey -- including 30 percent of those who said they'd be likely to use tPA in an ideal setting, and 29 percent of those who said they wouldn't. "It appears that individual anecdotal experience is influencing decision-making, when it should be the medical literature that leads the way," says Brown.

No matter what, Brown and her colleagues say, it will be important to find alternatives or additions to tPA. She cites current and planned clinical trials of drugs that may reduce the risk of hemorrhage, such as beta blockers or other adjuvant drugs, or new experimental clot-busters.

"According to those surveyed, risk from tPA would have to be cut in half before more doctors would use it," says Barsan. "Now, we need to get to that lower risk level. In the meantime, leaving the ED physician as the at-fault person is not what needs to be done. Just like with major trauma it's not just one doctor, it's a system -- and you need dedication and teamwork to have a system that works."

The study was funded internally by the U-M Health System. In addition to Brown and Barsan, the study's authors are Lynda Lisabeth, Ph.D., a research investigator in the U-M Department of Neurology; Lewis Morgenstern, M.D., director of the U-M Stroke Program and a stroke neurologist, and Michael Gallery, Ph.D. of ACEP.