TARGET: STROKE Cuts Door-to-Needle Time, Improves Outcomes

Susan Jeffrey

April 22, 2014

Not only did TARGET: STROKE, a new quality improvement program aimed at improving door-to-needle (DTN) times for patients with acute ischemic stroke, increase the number of patients receiving thrombolytic therapy in that time frame, but that improvement was associated with lower in-hospital mortality, less bleeding, and more patients discharged home.

"While there have been concerns that attempting to achieve shorter DTN times may lead to rushed assessments, inappropriate patient selection, dosing errors, and greater likelihood of complications, our findings suggest that more rapid reperfusion therapy in acute ischemic stroke is not only feasible, but can be achieved with actual reductions in complications and improved outcomes," said lead author Gregg C. Fonarow, MD, from the Division of Cardiology, University of California Los Angeles.

The program, recently implemented at Get With the Guidelines-Stroke (GWTG-Stroke) hospitals across the United States, saw median DTNs decline from 74 minutes in 2009 to 59 minutes in 2013, an absolute difference of 15 minutes (P < .0001).

Dr. Fonarow presented these results previously at the recent American Heart Association/American Stroke Association (AHA/ASA) International Stroke Conference 2014, and they are now published online April 22 in JAMA.

Also published in this neurology-themed issue of JAMA are 2 other studies relating to stroke practice.

In 1, researchers led by Martin Ebinger, MD, Charite-Universitätsmedizin Berlin, Germany, report results of the Pre-Hospital Acute Neurological Treatment and Optimization of Medical care in Stroke (PHANTOM-S) trial using a specialized ambulance dubbed the Stroke Emergency Mobile (STEMO) to decrease time to tissue plasminogen activator (tPA) treatment of patients with ischemic stroke.

Dr. Gregg C. Fonarow

The trial, presented in May 2013 at the XXII European Stroke Conference and reported by Medscape Medical News at that time, showed that use of the ambulance — which has an on-board computed tomography (CT) scanner, point-of-care laboratory, telemedicine connection, and specialized prehospital stroke team (including a neurologist, paramedic, and radiology technician) — was associated with a 25-minute reduction in patients receiving tPA. In addition, more patients received tPA than during control weeks when the ambulance was not deployed (33% vs 21%), with no increase in intracerebral hemorrhage or mortality.

In another stroke-related report, researchers examined whether it might be possible to presume consent for tPA treatment among patients with acute ischemic stroke.

Winston Chiong, MD, PhD, from the University of California, San Francisco, and colleagues examined presumption of consent by comparing preferences for treatment of acute ischemic stroke with thrombolysis and treatment of sudden cardiac arrest with cardiopulmonary resuscitation (CPR; in which the presumption of consent is generally accepted) in a nationally representative sample of US adults 50 years of age or older.

"In life-threatening emergencies involving incapacitated patients without surrogates, clinicians may intervene without obtaining informed consent, applying the presumption that reasonable people would consent to treatment in such circumstances," the researchers write. "Whether this rationale applies to the treatment of acute ischemic stroke with intravenous thrombolysis is controversial because this intervention improves functional outcomes but is not life preserving. Nonetheless, the presumption of consent to thrombolysis for ischemic stroke has recently been endorsed by professional societies."

Most adults surveyed — 76.2% (419 of 545 participants) — reported they would want thrombolytic therapy for stroke, similar to the 75.9% (422 of 555) who said they would want CPR for sudden cardiac arrest.

"When an incapacitated older patient's treatment preferences are unknown and surrogate decision makers are unavailable, there are equally strong empirical grounds for presuming individual consent to thrombolysis for stroke as for presuming individual consent to CPR. Because the presumption of consent is generally accepted for CPR, this finding provides empirical support for policy positions recently taken by professional societies that favor the use of thrombolysis for stroke in emergency circumstances under a presumption of consent," the authors write.


The proven benefits of tPA in stroke are highly time dependent, Dr. Fonarow noted, and current AHA/ASA guidelines, as well as other national and international guidelines, recommend DTN times of 60 minutes or less of patient arrival. "But despite all the evidence and guidelines and prior initiatives, prior studies have shown that less than 30% of patients who are treated with [intravenous] tPA are actually treated within this guideline-recommended goal," he said.

To address the problem, the TARGET: STROKE initiative was launched in 2010, with an initial goal of treating more than 50% of patients within that time frame. Best practices were identified; a comprehensive set of clinical and decision-support tools, including a time tracker, was rolled out; and all hospitals already participating in the AHA/ASA's GWTG-Stroke program were invited to participate, with opportunities for national recognition for the hospitals that achieved the goal.

The 10 best practices derived from literature review and published in 2011 by Dr. Fonarow and colleagues were as follows:

  • Hospital prenotification by emergency medical services

  • Rapid triage protocol and stroke team notification

  • Single call/paging activation for the entire stroke team

  • Use of a stroke tool kit, including clinical decision support, stroke-specific order sets, guidelines, hospital-specific algorithms, critical pathways, National Institutes of Health Stroke Scale, and other tools

  • Rapid acquisition and interpretation of brain imaging

  • Rapid laboratory testing (including point-of-care testing) when indicated

  • Premixing tPA for likely candidates

  • Rapid access to intravenous tPA in the emergency department/brain imaging area

  • Team-based approach

  • Rapid data feedback to stroke team on each patient's DTN time and other performance data

The current study sought to evaluate the results of implementation of the TARGET: STROKE program in participating hospitals and, further, to see whether these changes over time would result in improvements in patient outcomes, including in-hospital mortality, discharge destination, ambulatory status, the occurrence of symptomatic intracranial haemorrhage (ICH) up to 36 hours after administration of tPA, and overall complications related to treatment.

The study involved 71,169 patients with acute ischemic stroke treated at 1 of 1030 hospitals participating in GWTG-Stroke before and after implementation of TARGET-STROKE, comparing outcomes in 27,319 patients treated during 2003–2009 with those achieved in 43,850 treated during 2010–2013. They compared quarterly DTN times, adjusting for patient and hospital characteristics. Baseline demographics showed few clinically meaningful differences in patients or hospital characteristics before and after TARGET: STROKE implementation, "so there wasn't a shift in the population," Dr. Fonarow noted.

The percentage of patients with DTN times within 60 minutes increased from 29.6% in the fourth quarter of 2009 to 53.3% by the third quarter of 2013, "a highly statistically significant, clinically relevant improvement," he said (P < .001).

Median DTN times declined from 74 minutes before the intervention to 67 minutes after the intervention, again a highly statistically reduction (P < .001).

Clinical outcomes were also significantly improved in the postintervention period, including in-hospital all-cause mortality, without increased risk for ICH. The exception was independent ambulatory status, which was improved but not statistically significantly so. In fact, ICH occurred significantly less among treated patients.

Table. TARGET:STROKE: Clinical Outcomes Pre- vs Postintervention

Endpoint Preintervention (%) Postintervention (%) Adjusted Odds Ratio (95% Confidence Interval) P Value
In-hospital all-cause mortality 9.93 8.25 0.89 (0.83 - 0.94) <.001
Discharge to home 37.6 42.7 1.14 (1.09 - 1.19) <.001
Independent ambulatory status 42.2 45.4 1.03 (0.97 - 1.10) .31
Symptomatic ICH within 36 h 5.68 4.68 0.83 (0.76 - 0.91) <.001


The rate of increase in patients with DTN times of 60 minutes or less was 6.20% (95% confidence interval [CI], 5.58% - 6.78%) per each of 4 quarters after the intervention for TARGET: STROKE vs 1.36% (95% CI, 1.04% - 1.67%) per each of 4 quarters before intervention for TARGET: STROKE (P < .001 for comparison of the 2 slopes). A graph of the trend over time shows a sharp increase in the slope for patients treated within 60 minutes after the intervention.

Asked for comment on these findings when they were presented at the International Stroke Conference, Kyra Becker, MD, professor of neurology and neurological surgery at the University of Washington Medicine Stroke Center at Harborview, Seattle, said the improvements seen in this study underline the "power of quality improvement process: when you know your performance is being tracked, you get better," she told Medscape Medical News.

"It shows you the power of rewarding people for good behavior as well," she added. "When there is a target to achieve, people rise to achieve it."

The question arises of whether the improvement over time could be attributed to the evolution of stroke care, Dr. Becker noted. "But if you look at the slope of rise before the initiative, it was much lower than after the initiative, so I think clearly, the TARGET:STROKE initiative improved people's enthusiasm to get better faster."

Where and How to Direct Efforts

In an editorial accompanying the publications, James C. Grotta, MD, from Memorial Hermann Hospital, Clinical Innovation and Research Institute, Houston, Texas, comments on the 2 studies looking at strategies to improve time to tPA administration.

"The studies by Fonarow et al and Ebinger et al in this issue of JAMA indicate exactly where and how to direct efforts in improving treatment outcomes for patients with acute ischemic stroke—namely by reducing time from symptom onset to treatment," Dr. Grotta writes.

"Whatever benefits occur from interventions to achieve more rapid tPA treatment for patients with acute stroke need to be balanced against the costs to establish and maintain them, both to the payers who will pay for them and the hospital and emergency medical services organizations that will implement and operate them," he points out.

"This issue requires carefully constructed cost-effectiveness studies carried out in the environments where the interventions will be implemented; these are likely to differ between cities in the United States and in other countries and between rural and urban areas."

Dr. Ebinger and colleagues also note that the improvements they reported in the PHANTOM-S study have to be weighed against costs of the STEMO approach. Depending on the configuration of the vehicle, a single STEMO ambulance costs about $1.4 million. Cost-effectiveness analyses are currently under way, they add.

TARGET: STROKE is an initiative provided by the AHA/ASA. The GWTG-Stroke program is currently supported in part by a charitable contribution from Janssen Pharmaceutical Company. PHANTOM-S was funded by the Zukunftsfonds Berlin and the Technology Foundation Berlin with European Union cofinancing by the European Regional Development Fund. The study by Dr. Chiong and colleagues was supported by grants from the National Institute on Aging, the National Center for Advancing Translational Sciences, and funding through the American Brain Foundation Clinical Research Training Fellowship Program. Dr. Fonarow reported serving as a member of the GWTG steering committee; receiving significant research support from the National Institutes of Health; and being an employee of the University of California, which holds a patent on retriever devices for stroke. Dr. Grotta reported having received consulting fees from Specialists on Call, Frazer, and Stryker and grants from Genentech, Lundbeck, Haemonetics, Covidien, and Zoll. Dr. Ebinger and Dr. Chiong have disclosed no relevant financial relationships; disclosures for their coauthors are available in the papers.

JAMA. Published online April 22, 2014. TARGET:STROKE abstract PHANTOM-S abstract Chiong et al abstract Editorial


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