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In Historic Joint Policy Document, the AAN and ACEP Endorse Clinical Policy on tPA for Stroke



In a clinical policy document developed by a joint panel of members of the American Academy of Neurology and the American College of Emergency Physicians, the groups concluded that evidence supports the three-hour treatment window for using tissue plasminogen activator for stroke, as well a three- to 4.5-hour window in carefully selected patients meeting established treatment criteria. The joint policy document was in development for six years.

Emergency physicians and neurologists are now working from the same playbook when it comes to administering tissue plasminogen activator, or tPA, to improve functional outcomes for patients who have had an acute ischemic stroke (AIS).

In a clinical policy document developed by a joint panel of members of the American Academy of Neurology (AAN) and the American College of Emergency Physicians (ACEP) — which was published in the February Annals of Emergency Medicine — the groups concluded that evidence supports the three-hour treatment window approved by the US Food and Drug Administration, as well a three- to 4.5-hour window in carefully selected patients meeting established treatment criteria.

The timelines are in accord with recommendations issued in 2007 and updated in 2009 by the American Heart Association (AHA) Stroke Council, as well as the findings of the European Cooperative Acute Stroke Study III (ECASS III). [See more about the policy: “The AAN-ACEP Clinical Policy Document on tPA.”]

The policy document took six years to develop, said panel member Steven R. Messé, MD, assistant professor of neurology at the University of Pennsylvania Hospital's department of stroke and neurocritical care.

“What is important is that we did this together, and now we are all on the same page,” he told Neurology Today. “By collaborating we were finally able to reach these conclusions on appropriate treatment, and emergency physicians today have a strong statement they can follow.

“Our two specialties come from very different perspectives on tPA use and there has been some resistance, but most are very open to it,” he continued. “In emergency medicine there has been a loud but small minority who are opposed to the use of tPA because of the bleeding risk, but some neurologists have been reticent too.”

The policy document should be especially helpful in providing guidance for emergency physicians at smaller hospitals, especially those who have limited experience with tPA, who see fewer stroke patients, and those treating patients who live some distance away from the emergency room, he said.

“The important point is that these hospitals need a tPA treatment protocol and a system to care for these patients.”

“The three- to 4.5-hour is an option that should be considered because it reflects our best understanding at this time, but we were careful to say that it is not a best practice for all patients,” said panelist Andy S. Jagoda, MD, professor and chair of the department of emergency medicine and director of the emergency medicine department at Mount Sinai School of Medicine in New York City.

“It must be tailored to the individual, and the protective benefits decrease with time. Even in stroke centers it is important to select the best candidates. The ideal remains to administer tPA within the first three hours, and the sooner the better,” he told Neurology Today.

“Stroke care transcends specialties, and I think this statement demonstrates how better outcomes are dependent on multidisciplinary collaborations,” he told Neurology Today. “This collaboration is an important step toward integrating best practices and medical evidence between the two specialties charged with providing stroke care.”

Dr. Messé pointed out that with the growth of telemedicine there is an increasing amount of help available from experienced stroke centers, including video conferencing, to help emergency physicians make critical treatment decisions.


Since its approval, tPA has made slow but steady gains in emergency rooms across the country, but most patients are still not being treated. The most often cited reason is because they do not seek treatment in time. If treated within three hours, one in three patients who have had an AIS will either recover without symptoms or have major improvement in symptoms, according to the AHA.

However, in a recent study of nearly one million stroke admissions at hospitals participating in the AHA “Get With The Guidelines-Stroke” program, fewer than 5 percent of patients were eligible for tPA, largely because they arrived too late. The most critical obstacle to increasing tPA use and improving outcomes is patient awareness of stroke symptoms so that they seek medical care quickly, the AHA says.

But concern about the potential risk of hemorrhage in treated patients and potential malpractice claims, have also been barriers, especially among emergency room physicians seeing patients with comorbid medical conditions and those taking blood thinners. Bleeding in the brain is the most common risk with tPA, and occurs in 6 out of 100 patients, according to AHA statistics.

If every eligible ischemic stroke patient were treated according to the established AHA guidelines, the group estimates that stroke-related disabilities could be averted in hundreds of thousands of patients.


Sean I. Savitz, MD, professor of neurology at the University of Texas Medical School at Houston, called the collaboration “a landmark achievement” and a strong endorsement of the evidence for emergency rooms.

“I have never seen such an endorsement backed by such an excellent review of the evidence,” he told Neurology Today, adding that it is “a partnership that needs nourishing so that similar joint initiatives might address other health challenges in the future.”

Larry B. Goldstein, MD, professor of neurology and Director of Duke University Medical Center's Stroke Center, Durham, NC, said the ACEP policy statement should help increase tPA use.

“I think that this is a welcome alignment of recommendations regarding the clinical use of IV tPA between emergency medicine and neurology professional societies, and is consistent with American Heart Association/American Stroke Association evidence-based guidelines. This should importantly reduce any confusion among stroke emergency care providers and facilitate multidisciplinary patient care.”

“This has been long coming,” added Patrick D. Lyden, MD, chair of the department of neurology at Cedars-Sinai Medical Center, Los Angeles.

Dr. Lyden has conducted extensive research into potential treatments for stroke and led the pivotal 1995 study of tPA for the National Institute of Neurological Disorders and Stroke tPA Stroke Study Group.

“I feel this is a tremendous advance, and it will make a huge difference in how stroke patients are treated once they reach the emergency room,” he said.

The policy document was also endorsed by the Neurocritical Care Society and supported by the Emergency Nurses Association.


According to the new joint policy document from the AAN and the American College of Emergency Physicians, the highest level of clinical evidence for patient management (Class A) is administration within three hours of symptom onset in patients meeting the inclusion/exclusion criteria established by the NINDS, and that it should be “offered” to such patients. Such evidence reflects a high degree of clinical certainty, it said.

Class B evidence, reflecting moderate clinical certainty, supports a three- to 4.5-hour treatment window for patients meeting ECASS III inclusion/exclusion criteria, and such patients should be “considered.”

The document emphasized that the effectiveness of tPA has been less well established in hospitals lacking systems of care to safely administer tPA.

The US Food and Drug Administration approved tPA in 1996 if given within a three-hour treatment window, however a 2009 science advisory by the American Heart Association (AHA) Stroke Council widened the window to 4.5-hours in certain patients, based on the ECASS III findings.


• Clinical Policy: Use of intravenous tPA for the management of acute ischemic stroke in the emergency department; a collaborative project of the American College of Emergency Physicians and the American Academy of Neurology. Ann Emerg Med 2013;61:225–243.
    • Allen NB, Kaltenbach L, Goldstein LB, Regional variation in recommended treatments for ischemic stroke and TIA: Get With the Guidelines-Stroke 2003–2010. Stroke 2012;43:1858–1864.
    • Hacke W, Kaste M, Bluhmki E, et al. for the ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359:1317–1329.
    • Adams HP, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups. Stroke 2007;38:1655–1711.
    • The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. New Eng J Med 1995;333:1581–1587.
    • The AHA “Get with the Guidelines-Stroke” Program:
      • The NIH Stroke Scale:
        • The NINDS Stroke Research Priorities: