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Stroke Initiative Cuts tPA Administration Times, Improves Outcomes

Samson, Kurt

doi: 10.1097/01.NT.0000451010.48589.d0
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TIn a study of more than 1,000 hospitals and medical centers, door to needle (DTN) times for thrombolysis therapy for acute ischemic stroke fell from 77 minutes to 67 minutes at hospitals using the Target: Stroke practices, while DTN times of 60 minutes or less increased from 26.5 percent to 41.3 percent.

By following a quality improvement program and 10 key best practice strategies developed by the American Stroke Association, more than 1,000 hospitals across the United States reduced to near-target levels door-to-needle times for administering tissue plasminogen activator (tPA) to ischemic stroke patients.

The model reduced risk of in-hospital death and intracranial hemorrhage, and increased the number of patients being discharged to home rather than nursing care or similar facilities.

The study, which tracked tPA timelines and stroke outcomes in more than 71,000 stroke patients before and after initiation of the association's Target: Stroke program, found that following the improvement measures reduced the average door-to-needle (DTN) time for administering clot-dissolving tPA from 77 minutes to 67 minutes. The ideal target is one hour, which most participating hospitals did achieve in at least 50 percent of patients.

Led by Gregg C. Fonarow, MD, co-chief of the Division of Cardiology and the Eliot Corday chair in cardiovascular medicine and science at the University of California, Los Angeles Medical Center, the study involved 1,030 participating hospitals and medical centers.

The findings appeared in the April 23/30 issue of the Journal of the American Medical Association.

The researchers evaluated DTN data before and after initiation of the American Stroke Association's Target: Stroke program in 2010. They compared response times for 71,169 patients treated with tPA after Target: Stroke or under the Get With The Guidelines (GWTG) program, established by the American Heart/Stroke Association in 2000.

Target: Stroke includes 10 best practice strategies for achieving faster DTN times, as well as clinical decision support tools and encouragement of the sharing of best practices.

DTN times for fell from 77 minutes to 67 minutes at hospitals using the Target: Stroke practices, while DTN times of 60 minutes or less increased from 26.5 percent to 41.3 percent. In the third quarter of 2013, 53.3 percent of patients had DTN times of 60 minutes or less.

Earlier intervention translated into better outcomes as well. In-hospital deaths dropped from 9.9 percent to 8.3 percent, patients discharged home increased from 38 percent to 43 percent, and unassisted walking rose from 42 percent to 45 percent. Significantly, symptomatic intracranial hemorrhage within 36 hours fell from 5.7 percent to 4.7 percent, and there was a greater than four-fold increase in the early rate of improvement in patients with door-to-needle times of 60 minutes or less.

“Despite the evidence, national guideline recommendations, and prior quality improvement efforts, hospitals' initiation of tPA treatment was frequently beyond the recommended target of a door-to-needle time of 60 minutes or less prior to the initiation of the Target: Stroke Program,” Dr. Fonarow told Neurology Today in a telephone interview.

“In a prior analysis of GWTG-Stroke, only one-quarter of patients with acute ischemic stroke treated with tPA within three hours of symptom onset had door-to-needle times within 60 minutes, and little improvement was observed over a seven-year period,” he noted.

Among the practices that can speed delivery times are emergency medical services (EMS) ambulance teams collecting and forwarding patient details to the hospital while en route; using a single call to notify the entire stroke staff; pre-mixing tPA and storing it in the brain scanning area; and ongoing webinars to share more rapid response practices. He also said the Target: Stroke “honor roll” certification for hospitals that have achieved best DTN times also helps.

“Although there have been concerns that attempting to achieve shorter door-to-needle times may lead to rushed assessments, inappropriate patient selection, dosing errors, and greater likelihood of complications, our findings suggest that more rapid reperfusion therapy is feasible and, importantly, can be achieved not only without increasing rates of symptomatic intracranial hemorrhage, but also with reductions in complications.”

Target: Stroke will shortly launch a second phase in hopes of getting 75 percent of patients treated with DTN times within 60 minutes and 50 percent of patients treated within 45 minutes, Dr. Fonarow said.

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“This important paper demonstrates the utility of quality care initiatives for improving patient outcomes,” said Steven R. Messé, MD, FAAN, an associate professor of neurology in the Division of Stroke and Neurocritical Care at the Hospital of the University of Pennsylvania in Philadelphia.

“Time from stroke onset to treatment with tPA is the modifiable factor with the greatest impact on response to thrombolysis for acute ischemic stroke,” he told Neurology Today.

“Multiple prior studies have confirmed that earlier treatment leads to better outcomes. The gains in treatment times following the Target: Stroke initiative translated into meaningful increases in the number of patients discharged home, and reductions in symptomatic hemorrhage and mortality,” he noted.

“That said, there is clearly still room for improvement in acute stroke care in the United States and additional efforts should continue in this area.”

Atte Meretoja, MD, PhD, of the department of neurology at Helsinki University Central Hospital in Finland, and the Melbourne Brain Centre at the Royal Melbourne Hospital in Victoria, Australia, told Neurology Today that to achieve a reduction in DTN times on such a scale “is a remarkable achievement.”

In 2012, Dr. Meretoja and colleagues published a prospective study in Neurology in which they reported reducing median DTN times to just 20 minutes in 1,860 stroke patients at one large hospital in Helsinki, by using many of the interventions that were also used in the Target: Stroke program. In addition, they used ambulance pre-notification with patient details, allowing the hospital to access past medical history during transport; transferring patients directly from triage to CT on the ambulance stretcher; and delivering tPA in the CT room immediately after imaging. In another study, published in Neurology the following year, he and his colleagues reported that the “Helsinki model” reduced DTN times at the Royal Melbourne Hospital in Australia to 25 minutes in just four months, demonstrating that the model could work at other medical facilities treating stroke patients.



“These new findings in the US represent a huge effort and one of the largest quality improvements in the entire world,” Dr. Meretoja told Neurology Today.

“They had 1,000 hospitals, and to cut median DTN by 15 minutes is quite remarkable. I think it shows that this is an excellent program in getting people to work together,” he said. “When the GWTG initiative was introduced, physicians were still a bit wary of tPA, but now seem to be moving together in the right direction. There have been a lot of papers published on streamlining of stroke thrombolysis and we are getting the same message from all directions.”

Dr. Meretoja also noted that there is more benchmarking of tPA delivery times everywhere. “This is a good thing, because medical centers are now competing against each other — but the truth is that each hospital and center is really competing against themselves for the benefit of the patient. It is all about building a team and encouraging teamwork. And by this I also include the ambulance crew who are a crucial part of the team. When the ambulance personnel take the patients to the right hospitals and pre-notify the hospitals with patient details, then the hospital can deliver the therapy so quickly that the ambulance crew gets to see the imaging, see the therapy, and be involved in team.”

In a third paper “Save a Minute, Save a Day,” published this year in Stroke, Dr. Meretoja and his colleagues quantified patient lifetime benefits gained from faster DTN in a modeling study conducted in Finnish and Australian centers.

They reported that each 15 minute decrease in delays provided an average equivalent of one month of additional disability-free life.

“In practice the GWTG Target: Stroke program has provided an additional month of life for each treated patient on top of the previous thrombolysis efficacy. With tens of thousands of patients treated, that is a huge heath gain with little or no cost. We are making great gains, but there is still much to do.”

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For an overview of the guideline recommendations, evidence-based strategies, and the 10 key practices to reduce door-to-needle times for intravenous rt-PA in eligible patients with acute ischemic stroke, visit

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•. Fonarow GC, Zhao X, Smith EE, et al. Door-to-needle times for tissue plasminogen activator administration and clinical outcomes in acute ischemic stroke before and after a quality improvement initiative. JAMA 2014;311:1632–1640.
•. More about Get with the Guidelines-Stroke:
    •. Grotta JC. tPA for stroke: important progress in achieving faster treatment. JAMA 2014;311(16):1615–1617.
      •. Meretoja A, Strbian D, Mustanoja S, et al. Reducing in-hospital delay to 20 minutes in stroke thrombolysis. Neurology 2012;79(4);306–313.
        •. Smith E, von Kummer R. Door-to-needle times in acute ischemic stroke: How low can we go. Neurology 2012;79(4):296–297.
          © 2014 American Academy of Neurology