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Skip Navigation LinksHome > August 2008 - Volume 30 - Issue 8 > With No Resolution on tPA, Debate Moves on to Stroke Centers
Emergency Medicine News:
doi: 10.1097/01.EEM.0000337982.13880.79
Special Report

With No Resolution on tPA, Debate Moves on to Stroke Centers

Munasque, Angela

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For more than a decade, the buzz in emergent stroke care has been fueled by three letters: tPA. The discord among physicians and physician organizations about the use of thrombolytics is still very much at the heart of the matter, but tPA isn't the be-all, end-all of stroke care, emergency physicians say.

The results of the National Institute of Neurological Disorders and Stroke (NINDS) trial on tissue plasminogen activator were published in 1995, and since then it's been lauded as a landmark study time and again by almost everyone but emergency physicians. (N Engl J Med 1995; 333[24]:1581.) The most recent American Heart Association (AHA) guidelines, supported by the American Academy of Neurology (AAN), recommend intravenous rtPA for selected patients within three hours of ischemic stroke onset. (Stroke 2007;38[5]:1655.)

“I think it took awhile after tPA was first shown to be beneficial in 1995 for the entire medical community to accept it as a beneficial treatment,” said Maarten G. Lansberg, MD, PhD, an assistant professor of neurology and neurological sciences at the Stanford Stroke Center in Palo Alto, CA. “But I'm talking from a neurology perspective.”

From an emergency medicine perspective, the American Academy of Emergency Medicine and the Society of Academic Emergency Medicine unequivocally state that tPA is not standard of care due to insufficient evidence concerning risk and benefit. The American College of Emergency Physicians' position statement also cites insufficient evidence for tPA as standard of care “when systems are not in place to ensure that inclusion/exclusion criteria…are followed.” ACEP is currently reviewing its clinical policy on stroke, but it won't be finalized until the end of this year or early 2009.

W. Richard Bukata, MD, a clinical professor of emergency medicine at Los Angeles County-USC Medical Center, is quick to point out the discrepancy between the medical groups. “So what we have, honestly, is a disagreement between all the emergency physician organizations and the American Heart Association and the American Academy of Neurology,” he said.

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Stroke Centers

This divide between physicians isn't new. (EMN 2005;27[2]:18; 2006;28[4]:16.) But its import in stroke care hasn't diminished. The newest controversy now is the diversion of stroke patients from local hospitals to a regional stroke center, according to Dr. Bukata, where patients are more likely to receive tPA.

Reports corroborate Dr. Bukata's assessment. IV tPA administration increased at the University of California-Irvine after it received primary stroke center certification for 10 patients a year, up from three, from the Joint Commission in 2004. (Neurology 2007;68[6]:469.) At a suburban hospital in Maryland, there was a sevenfold increase in the proportion of stroke patients treated with tPA in the first two years after it received primary stroke center status. (Stroke 2003;34[6]:e55.) In 32 hospitals in New York City, tPA utilization increased from 2.4 percent to 5.2 percent after stroke center designation. (Neurology 2006;67[1]:88.)

The problem isn't where the patients are being treated; it's that tPA hasn't been shown to be any more efficacious or safer than before. “There's been no new data since the NINDS trial that have looked at this,” Dr. Bukata said. “Twelve percent of the people got benefit, and six percent were harmed, and that is a bit like medical Russian roulette. We have virtually no other drugs in the hospital where the risk-benefit ratio is so close.”

In the NINDS trial, 12 percent of the group that received tPA had minimal or no disability, compared with the placebo group, but 6.4 percent of patients given tPA suffered an intracerebral hemorrhage within 36 hours. (N Engl J Med 1995;333[24]:1581.) In addition, Dr. Bukata noted that the NINDS trial was relatively small — 624 patients — and has never been repeated.

Figure. Dr. Maarten ...
Figure. Dr. Maarten ...
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Thrombolytic therapy is used readily when deemed appropriate at the Stanford Stroke Clinic, but Stanford experts recognize the potential dangers of tPA and exercise caution, according to Dr. Lansberg. “It certainly is not an effective way to treat all stroke patients, and the main limitation is that the majority of patients don't come in on time to be treated,” he said. “We still use fairly strict criteria to determine if a patient is eligible.”

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Beyond Thrombolytics

There's more to stroke centers than thrombolytics, however, Drs. Lansberg and Bukata agreed. There are 491 primary stroke centers across the nation certified by the Joint Commission, chosen using the Brain Attack Coalition's recommendations. (JAMA 2000;283[23]:3102.) Written care protocols, acute stroke teams, and integrated emergency response systems are three of the 11 elements of a primary stroke center, with the aim to get patients to treatment as efficiently as possible. In New York, stroke center designation decreased door-to-physician times from an average of 25 minutes to 15. (Neurology 2006;67[1]:88.)

While acute treatment is one aspect of stroke centers, prevention of immediate complications such as deep vein thrombosis and aspiration pneumonia and prevention of subsequent strokes are equally important goals, said Dr. Lansberg. The University of California-Irvine report showed that Joint Commission stroke center certification was associated with an increase in lipid profile testing (71% before vs. 86% after) and DVT prophylaxis (80% before vs. 98% after) at its institution. (Neurology 2007;68[6]:469.)

Dr. Bukata acknowledged the comprehensive care that stroke centers offer. “The data, according to my read on it, on stroke centers are that patients do better when they are treated at a stroke center,” he said. “It's not that they do anything that is particularly miraculous, but they have coordinated care that focuses on all of the necessities that need to be addressed in patients who've had strokes. It's done consistently; it's done well, by people who are interested in the subject.” These “low-tech” approaches include early ambulation, avoiding Foley catheters, and early physical and speech therapy.

In addition, the Stanford Stroke Center (http://strokecenter.stanford.edu) provides a unique component of stroke care: their TIA clinic, launched in August 2006, where patients presenting to the ED with TIA symptoms are treated on an urgent outpatient basis. Once an EP sees the patient, he consults the neurology team, who will evaluate the patient using the ABCD2 scale (Lancet 2007;369[9558]:283) to determine the stroke risk at two days and one week, according to Connie Wolford, RN, the TIA Clinic coordinator. Patients deemed low risk for an imminent stroke are discharged home, and come back in one to two business days for an outpatient MRI and clinic visit.

The TIA Clinic benefits patients and the hospital alike. Patients “don't have to sit and wait in the hospital. It's a nice way to send them home, to be in the comfort of their home with their families, and come back for tests,” Ms. Wolford said. And for hospitals, this practice is “cost-effective, and frees up a lot of hospital beds, an issue for hospitals across the country,” she said.

Established in 1992 and accredited by the Joint Commission in 2004, the Stanford Stroke Center cares for more than 2000 patients and boasts specialists in emergency medicine, neurology, and rehabilitation, but also a specialized support staff of dietitians and medical social workers. The center, part of a larger research institution, also conducts stroke research, and has designed or participated in more than 100 clinical trials.

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International Research

Around the world, stroke research is being conducted on making thrombolytics safer, subsequent stroke prevention, and new treatment approaches, such as telemedicine. Because one of the main complaints about tPA use, especially among emergency physicians, is the high risk of intracerebral hemorrhage and the lack of benefit, more knowledge on how to better select patients is desirable. (Ann Emerg Med 2005;46[1]:56.) Magnetic resonance imaging appears to be one potential answer. A recent Korean study suggests that thrombolysis based on MRI criteria may be safely applied to acute stroke patients with unclear onset. (Cerebrovasc Dis 2008;25[6]:572.)

Research out of China suggests that hyperacute ischemic cerebral infarction patients who are strong candidates for IV thrombolytics can be identified with multiparametric protocol MRI, especially those whose time windows were beyond the current standard of three hours. Of 77 patients evaluated, 12 received tPA and showed clinical improvement, but one developed an asymptomatic intracranial hemorrhage three weeks after treatment. (Neurol Res 2008;30[4]:344.)

For subsequent stroke prevention, pharmacological and surgical approaches are being investigated. In the recently completed Warfarin vs. Aspirin for Symptomatic Intracranial Arterial Stenosis trial, aspirin was found to be superior to warfarin in preventing subsequent strokes and other vascular-related events. (New Engl J Med 2005;352[13]:1305.) The ongoing Carotid Occlusion Surgery Study, led by researchers at the University of North Carolina, is currently recruiting patients to determine if extracranial-intracranial bypass surgery when added to best medical therapy can reduce the subsequent risk of ipsilateral stroke in high-risk patients. (http://clinicaltrials.gov/ct/show/NCT00029146.) The ongoing Insulin Resistance Intervention after Stroke (IRIS) trial led by Yale University researchers is examining if pioglitazone, a drug for type 2 diabetes, is effective in lowering the risk for subsequent stroke and heart attack in those who have developed insulin resistance. (http://clinicaltrials.gov/ct/show/NCT00091949.)

And while primary stroke centers are plentiful in California, home to 45 Joint Commission certified institutions, they are much more sparse in other regions of the United States, such as the “stroke belt,” a term for the southeastern part of the nation, which has had the highest stroke mortality rates in the country for decades, according to the Centers for Disease Control and Prevention. Currently, there are three stroke centers in Alabama, two each in Louisiana and Arkansas, and one in Gulfport, Mississippi.

In areas where patients don't often have the option for specialized stroke care, telemedicine might come in handy. A German study analyzed the use of telemedicine for stroke care among two stroke centers and 12 regional general hospitals from 2003 to 2005 and found that the majority of teleconsultations were requested beyond normal working hours and that a significant proportion had an impact on clinical decisions, such as nonstroke diagnoses or the use of thrombolysis. (Cerebrovasc Dis 2008;25[4]:332.)

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Until Then

The list of stroke research goes on and on, literally: www.strokecenter.org/trials, but in the meantime, individuals will continue to have strokes, and they must be treated, despite differing opinions on thrombolytics, regardless whether there is a stroke center, and even though experimental approaches are still being tested. So what do emergency physicians do in the meantime?

For one, consistently and efficiently performing the low-tech tasks crucial to stroke care — again, early ambulation, timely radiological exams, avoiding Foley catheters — is top priority, according to Dr. Bukata. And while he is not a “big advocate of tPA,” he said he believes in informing the patient or his family of all their options and letting them decide. “They need to be told the risks and benefits of the proposed therapy, risks and benefits of alternative therapy, and the risks and benefits of doing nothing,” he said.

Dr. Bukata wants the best of both worlds. “When I have my stroke, I want to go to a stroke center,” he said, with qualification. He wants the multidisciplinary coordinated care of a stroke center without the thrombolytics typically given in the three-hour window. “I want to be taken to the closest hospital. I want to wait at that closest hospital for an hour, an hour and a half, and then I want to be sent to the stroke center.”

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The Rest of the Story on EM-News.com

To read more about stroke, visit the Exclusive Online Content section of EM-News.com. The site has links to the Stanford Stroke Center, the Carotid Occlusion Surgery Study, the Insulin Resistance Intervention after Stroke trial, the Stroke Trials Registry of the Internet Stroke Center at Washington University, and the full stroke policy statements of ACEP, SAEM, AAEM, and the AHA/AAN.

© 2008 Lippincott Williams & Wilkins, Inc.

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