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New Large Analysis Finds More Rapid Use of tPA for Stroke Leads to Better Outcomes

Kreimer, Susan

doi: 10.1097/01.NT.0000432678.07009.07
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A new study examining the outcomes of more than 50,000 acute ischemic stroke (AIS) patients found a 4 percent improvement in outcomes for every 15-minute interval of quicker therapy initiation.

A new study examining the outcomes of more than 50,000 acute ischemic stroke (AIS) patients confirms that speed is of the essence in delivering clot-busting treatment.

The major analysis led by Jeffrey L. Saver, MD, director of the University of California, Los Angeles (UCLA) Comprehensive Stroke Center, found a 4 percent improvement in outcomes for every 15-minute interval of quicker therapy initiation, according to a June 19 report in the Journal of the American Medical Association.

Until this study, limited information existed to link patient outcomes to the specific timing of administering tissue plasminogen activator (tPA) sooner rather than later, with data drawn from a series of small, randomized clinical trials.

The UCLA-led team utilized an extensive national registry representing clinical practice and including 58,353 acute ischemic stroke patients given tPA within 4.5 hours of onset. The Get With The Guideline–Stroke database was developed by the American Heart Association and American Stroke Association to support continuous quality improvement in hospital systems encountering patients with stroke and transient ischemic attack.

Information in the database spanned 1,395 hospitals between April 2003 and March 2012. The median age of patients — almost an even number of men and women — was 72; average time from stroke to start of treatment was 144 minutes.

Dr. Saver, also professor of neurology in the David Geffen School of Medicine at UCLA, told Neurology Today: “With the recent upgraded endorsement of tPA therapy by the leading American emergency medicine societies, neurologists and emergency physicians are now poised to work together to accelerate lytic therapy, and, based on the findings of this study, thereby help more acute stroke patients.”

Philip B. Gorelick, MD, MPH, medical director of the Hauenstein Neuroscience Center at Mercy Health in Grand Rapids, MI, said the new UCLA-led analysis “provides a mega experience with tPA in acute ischemic stroke. The findings support a clear mandate to accelerate onset-to-treatment time in acute ischemic stroke when tPA administration is being contemplated.”

Dr. Gorelick, also professor of translational science and molecular medicine at Michigan State University College of Human Medicine in Grand Rapids, added that “the main message carried forward by the authors is that rapid tPA administration (e.g., 0-90 vs. 181-270 minutes) is associated with reduced mortality and symptomatic intracranial hemorrhage, and more discharges to home and independence of ambulation.”

The investigators reported that “every 15-minute acceleration in start of tPA after onset was associated with patients having a 4 percent greater odds of walking independently at discharge, a 3 percent greater odds of being discharged to home rather than an institution, a 4 percent lower odds of death before discharge, and a 4 percent lower odds of experiencing symptomatic hemorrhagic transformation of infarct.”

Jeffrey A. Switzer, DO, associate professor and director of the Comprehensive Stroke Center at the Medical College of Georgia in Augusta, told Neurology Today that these differences may seem like small percentages, but they are clinically significant. The results reinforce the importance of educating the public about stroke symptoms and calling 911 emergency medical services, while urging hospitals to pinpoint symptoms for rapid triage and treatment of potential stroke patients.

Reduction of stroke onset to treatment delays also captured attention at the American Stroke Association's 2013 International Stroke Conference in February. A secondary analysis of the Interventional Management of Stroke (IMS) III Trial showed that each 30-minute delay in endovascular therapy resulted in an estimated 10 percent relative reduction in a good outcome.

“There have been several large post-approval registries that have demonstrated the safety of IV tPA in routine clinical practice in a variety of hospitals of different size,” said Dr. Switzer, who is also director of telestroke and teleneurology at Georgia Regents University in Augusta.

Steven R. Brenner, MD, former associate professor in the department of neurology and psychiatry at Saint Louis University School of Medicine, said streamlining the evaluation and treatment process remains a high priority. With this in mind, hospitals have been adapting emergency departments for acute stroke management by placing brain imaging equipment in those areas for swifter access.

“Even the best outcome is somewhat discouraging in that only about 30 percent of patients were ambulatory at discharge,” Dr. Brenner told Neurology Today. For this reason, “the doctor confronting the acute stroke patient in the emergency department has very serious decisions to make, with reference to lytic therapy, or tPA.”

An emphasis on protective measures — including better management of blood pressure and heart disease — is still the best defense. “It's much better to prevent strokes,” he said, “since treatment is very difficult once a stroke occurs.”

Dawn O. Kleindorfer, MD, professor and Vascular Neurology Division director at the University of Cincinnati College of Medicine, said teaching family members of patients to become more familiar with stroke symptoms also may help reduce treatment delays.

“When we look at the time intervals, the largest delay by far is patient recognition and making that initial call,” said Dr. Kleindorfer, co-director of the institution's stroke team. A patient hoping that numbness will subside with proper rest may be unaware that a stroke is already in progress.

For years, Dr. Kleindorfer has been “passionate” about enhancing public knowledge of stroke warning signals. Dissemination of simple mnemonics such as the Face Arm Speech Test (FAST) can resonate with people who otherwise may ignore telltale signs, so she recommends that neurologists use a compelling graphic to impart this message to patients and their loved ones. The FAST mnemonic is among the effective interventions mentioned in the UCLA-led analysis.

The JAMA study authors also credited regional stroke care systems with accelerating treatment. There, they noted that “prehospital personnel are trained to recognize stroke using validated screening tools, deliver patients at highest transport priority directly to certified stroke centers capable of delivering lytic therapy reliably and rapidly, and provide prearrival notification from the out-of-hospital setting to activate stroke teams and permit readying of computed tomographic or magnetic resonance imaging scanners for immediate use upon patient arrival.”

Overall, Dr. Kleindorfer summed up the new analysis as a broad and very strong demonstration that “faster treatment of standard accepted therapy is better.” Ultimately, “these small differences in time can make a big difference in the outcome.”

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•. Saver JL, Fonarow GC, Smith EE, et al. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA 2013: 309(23):2480-2488.
•. Neurology Today: “In Historic Joint Policy Document, the AAN and ACEP Endorse Clinical Policy on tPA for Stroke”:
© 2013 American Academy of Neurology