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Skip Navigation LinksHome > August 2009 - Volume 31 - Issue 8 > Rethinking tPA for Stroke
Emergency Medicine News:
doi: 10.1097/01.EEM.0000359183.90853.7e
Special Report

Rethinking tPA for Stroke

SoRelle, Ruth MPH

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The American Heart Association extends the tPA treatment window for stroke to 4.5 hours, and emergency medicine societies reconsider their objections to thrombolytics for stroke

Emergency physicians have long been among the most vociferously opposed to tPA for stroke, but some are now reconsidering that stance. Most notable in that group is the Society of Academic Emergency Medicine, whose Board of Directors officially “retired” its policy questioning the use of thrombolytics in patients with acute ischemic stroke in January. The action came at the behest of its Neurological Interest Group, which cited several phase IV trials that buttressed the argument for giving the drug.

In a letter to Yu-Feng Yvonne Chan, MD, the interest group's leader and an associate professor of emergency medicine at Mount Sinai School of Medicine in New York City, Katherine L. Heilpern, MD, the president of SAEM, and Jill M. Baren, MD, SAEM's president-elect, applauded the passion of the interest group in “advancing the science surrounding the best care of patients with acute neuroinjury.”

It is a stunning turnaround from the tumult surrounding the use of the clot-buster in stroke just six years ago when all of the major professional emergency medicine organizations — the American College of Emergency Physicians, the American Academy of Emergency Medicine, and SAEM — passed similar policies of no confidence in the emergency use of thrombolytics for stroke. ACEP is now reviewing its policy statement to determine if revisions are needed, according to Rhonda Whitson, the group's clinical practice manager. “ACEP is also working on the development of a clinical policy on acute brain ischemia, which includes a critical question related to the use of IV tPA for acute ischemic stroke,” she noted.

AAEM has not changed its policy, said the group's former president Robert McNamara, MD. He said the issue remains controversial, and will become more so as information emerges.

“I think many emergency physicians, especially those of us interested in stroke and neurological emergency, feel that the climate has changed,” said Dr. Chan. “In the past, many emergency physicians were nervous about the use of thrombolytics, and wanted more scientific proof that they are effective,” she said. The European Cooperative Acute Stroke Study III (ECASS III) showed that tissue plasminogen activator improved the clinical outcome in patients with acute ischemic stroke when administrated between three and 4.5 hours after the onset of symptoms. “The time is ripe for a change,” said Dr. Chan. “That applies especially to SAEM, which should be on the forefront of supporting evidence-based results.”

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Physician Attitudes

The change in attitude was clear to Phillip A. Scott, MD, an associate professor of emergency medicine at the University of Michigan Medical School, who surveyed emergency physician attitudes about acute stroke treatment as part of the INSTINCT trial, designed to evaluate a standardized, educational intervention in increasing appropriate tPA use in stroke.

In a study presented in May 2008 at SAEM's annual meeting, Dr. Scott and his colleagues found that 83 percent of the 199 emergency physicians who completed the survey would use tPA in an ideal setting. Seventy-two percent said its use in eligible patients represented ideal care but was not a legal standard of care while 27 percent said its use was ideal care and the legal standard. Forty-nine percent said existing data on the use of tPA in stroke are convincing, but 65 percent said they were uncomfortable treating without consultation. Sixty-six percent said a telephone consult was sufficient. Fifty-nine percent said they were concerned about the liability of not using tPA. On a 15-item test of knowledge about tPA, the median score was eight correct answers.

Ninety-six percent cited late patient arrival at the emergency department as a barrier to using tPA, while 42 percent cited a barrier as lack of access to a stroke team. Other barriers to care cited were emergency physician belief that tPA is beneficial (40%), no available neurologist (37%), no ability to maintain tPA treatment skills (33%), malpractice concerns (30%), lab results (25%), CT scan results (22%), and family or patient refusal (18%).

“I think it shows a substantial difference in the opinions of a broad cross-section of emergency physicians compared with four or five years ago,” said Dr. Scott. “There remain patient-related barriers in that 95 percent of patients are still presenting to the emergency department too late. And even when they do [present in time], often the emergency physicians report that 85 percent of the time there are insufficient data to establish when the stroke started.”

Dr. Chan echoed the concern of physicians who had no readily available support. Using thrombolytics is just not feasible in some places.

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Longer Treatment Window

In late May, a new advisory from the American Heart Association said extending the treatment window from three hours to 4.5 hours might provide some benefit to ischemic stroke patients. The study referred to the results of the ECASS III trial that appeared in September 25, 2008, New England Journal of Medicine. (359 [13]:1317.) Although symptomatic intracerebral hemorrhage was higher in treated patients, the rate was not higher than previously reported in patients treated in the three-hour period, and was not associated with a higher death rate.

The advisory group did not suggest that current tPA guidelines be changed, but urged more research to confirm the results of the trial.

While Gregory del Zoppo, MD, an adjunct professor of hematology at the University of Washington School of Medicine, stressed that tPA is only approved for use during the three-hour window and that patients with stroke need to get to the emergency department as soon as possible, he said this information should not be viewed as an attempt to bring more patients into treatment. “It is a reflection of the biology of ischemic injury in the brain,” said Dr. del Zoppo. “There are patients whose evolution of injury may be slower or different from others. If one knew how to select the patients discretely enough, one could find patients who would improve.”

The advisory notes that some patients should not be treated in the larger time window, including those over 80, those with severe stroke, those with a prior history of stroke and diabetes, or those on oral anticoagulants. “This is not as much expanding the time window [as] selecting patients using important criteria,” said Dr. del Zoppo, adding that he is concerned that patients might see the advisory as permission to wait longer to come to the emergency department. “There is no way to change the need for patients to come in as soon as possible,” he said. “They cannot wait an extra hour.”

He pointed out that the advisory is written conservatively. “We have some reservations,” he said. “The FDA or independent groups need to verify the data.”

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New Reality

More than that, institutions and regions need to look more carefully at how to make emergency therapy a reality. Charles Wira, MD, an assistant professor of emergency medicine and a liaison with the Yale-New Haven Stroke Program, and his colleagues sought to set up an interdisciplinary stroke program to coordinate care between emergency physicians and neurologists. They hoped that providing attending stroke coverage around the clock could increase the number of patients receiving emergency care for stroke.

Four neurologists and one emergency physician provided 24-hour on-call coverage within six hours for all stroke codes. Education about stroke and stroke care became more inclusive, and an emergency department liaison position was created and filled by an attending emergency physician.

In the year before the new stroke program, 230 stroke codes were called within the six-hour window at Yale-New Haven Hospital, and 19 patients received tPA. In the first year of the new service, 300 strokes were called with 33 patients receiving tPA.

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“It reinforces that changes were made here,” said Dr. Wira. “The objective first and foremost was to benefit the patients. It demonstrates a collaboration between two departments, emergency medicine and neurology,” he said.

The improvement in statistics “is probably a combination of increased awareness and the improved faculty support that contributed to more stroke alerts being called in the six-hour window. Overall, the numbers of patients coming in with stroke did not change,” said Dr. Wira.

In the future, he said he hopes stroke alerts receive the same response as trauma alerts with the same kinds of resources activated. “It is something we are seeing come to fruition already,” he said.

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EMS Protocols

Regionalization of stroke treatment might also prove beneficial, said Jeremiah Schuur, MD, an instructor in emergency medicine at Harvard Medical School and Brigham and Women's Hospital in Boston. While national groups have called for the regionalization of such care, a study by Dr. Schuur and his colleagues on laws and regulations governing such efforts in the United States showed spotty progress at best. Twenty-six states had statewide emergency medical services protocols for dealing with emergency stroke care, another 21 provided information on regional protocols, and information for four states was incomplete. Their findings showed:

▪ The emergency medical services protocols in 18 states included use of a stroke scale to assess patients before they got to the hospital.

▪ Nine states allow or require EMS to bypass the nearest hospital for one that has a stroke center.

▪ Eight states have regulations for defining primary stroke centers.

▪ Florida, Massachusetts, Maryland, and New York have fully integrated regionalized stroke protocols that involve use of a stroke scale and EMS bypass to a primary stroke center.

▪ No state regulations define receiving centers for patients with ST-segment elevated myocardial infarctions or regionalized STEMI care.

“This is purely a policy review,” said Dr. Schuur. “We don't have data to say what is most effective.” Major concerns revolve around whether such a system works best when it's regional or local.

“Most people think of regionalization as a way to make sure the right patients get to the right hospitals. Some hospitals might not be able to provide the services needed,” he said.

Those concerned about regionalization point out that the one-size-fits-all approach doesn't work. “In a rural community, there may be only a few ambulances available. If the nearest stroke center is a mile away, transporting a patient with stroke symptoms takes emergency medical services out of action for a long period of time,” Dr. Schuur said. Stroke symptoms also may mean that a lot of patients go to the stroke center, potentially overwhelming it. And many of those patients will not have a stroke, he said.

The first recommendations about the use of thrombolytics were promulgated in 1996, but they are not the end of improvements in care, said Laurence Katz, MD, an associate professor of emergency medicine at the University of North Carolina School of Medicine in Chapel Hill. His work with neurogenesis in the adult brain gives researchers hope that these cells might be valuable in treating brain injuries like those seen in stroke.

Dr. Katz began his work with adult liver stem cells that “will grow into whatever you want, depending on where you put them,” he said. “We decided to put them in the brain to see if they form neurons. Not only do these cells appear to change from liver to brain, but in preliminary studies, rats treated with these cells seem to regain near normal cognitive function within weeks after injury.” While much remains to be determined, Dr. Katz said this work could find future treatments for stroke and other brain injuries.

Comments about this article? Write to EMN at emn@lww.com.

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Viewpoint: tPA for Stroke?

The latest European Cooperative Acute Stroke Study has so many flaws, says Dr. Mark Mosley, that he wonders if it was intentionally deceptive. See p. 5.

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EMN Online

Read the policies and advisories referred to in this article on EM-News.com. Go to EMN Online for August, and click on EMN FastLinks.

© 2009 Lippincott Williams & Wilkins, Inc.

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