ISC 2009: Stroke Patients Arriving Within "Golden Hour" More Likely to Get tPA

Susan Jeffrey

February 19, 2009

February 19, 2009 (San Diego, California) — A greater proportion of patients who arrive at the hospital in the first 60 minutes after symptom onset — the so-called "golden hour" — receive thrombolytic therapy than those who arrive later, new data from the Get With The Guidelines-Stroke (GWTG-S) quality-improvement program shows.

In this analysis, 12% of all ischemic stroke patients seen at 100 GWTG-S hospitals arrived within 1 hour of symptom onset, and 27.1% of these were treated with tissue plasminogen activator (tPA) vs 12.9% of those arriving between 1 and 3 hours after onset.

However, Jeffery L. Saver, MD, from the University of California, Los Angeles Stroke Center, pointed out that golden-hour patients also had door-to-needle (DTN) times that were about 20 minutes longer than those arriving later, and only about 20% were treated within 60 minutes of arrival.

"These findings support greater public-education efforts to increase the proportion of patients arriving in the first 60 minutes after symptom onset and a revamping of our hospital's performance-improvement activities to shorten the DTN times in patients who've done their part in arriving in the first 60 minutes, to make sure we do our part and get drug started for them in the next 60 minutes," Dr. Saver concluded.

He presented their findings here at the American Stroke Association International Stroke Conference 2009.

Benefit Strongly Time Dependent

The benefit of intravenous (IV) tPA in acute ischemic stroke is strongly time dependent, Dr. Saver said. Therapeutic yield of treatment is maximal in the first minutes after stroke and declines steadily during the first 3 hours. "Every minute that goes by without treatment, 2 million nerve cells die," he said. "Every 10 minutes that goes by without tPA, 1 fewer patient experiences benefit from tPA."

Patients who present within the first 60 minutes after symptom onset have the greatest opportunity for benefit from treatment, but these patients have not been well characterized. "That's why we undertook this study," Dr. Saver said.

They used the GWTG-S registry, a national database of acute strokes treated at participating hospitals in the United States. From 905 participating hospitals, a total of 517,000 stroke and transient ischemic attack patients were entered in the database between April 2003 and December 2007. After excluding those who did not arrive directly at the emergency department by ambulance or private vehicle, those having hemorrhagic strokes, and patients for whom a time of symptom onset could not be documented, they were left with 106,924 patients for this analysis.

Of these, 28.3% arrived at the hospital within 60 minutes of symptom onset; the mean onset-to-door time for these patients was 39.9 minutes.

Onset-to-Door Times for Stroke Patients Arriving Directly to GWTG-S Hospitals

Time (min) n %
< 60 30,220 28.3
61 – 180 33,858 31.7
> 180 42,846 40.1

Although most patient characteristics examined were to some extent statistically significant, 2 factors stood out; National Institutes of Health Stroke Scale (NIHSS) score, which was higher in those arriving earlier (8 for those arriving within 60 minutes vs 4 in those arriving after 3 hours), and arrival by ambulance, which was the case in 79% of those arriving in the golden hour, vs 55% of those arriving after 3 hours.

Overall, 11.8% of all ischemic stroke patients arriving directly at the hospital with a documented onset time were treated with IV tPA, vs 5% of those without a documented onset of symptoms. The mean onset-to-door time in patients who received tPA was 56 minutes, and the mean DTN time was 84 minutes.

Those arriving within the golden hour were much more likely than those arriving later to receive thrombolysis, Dr. Saver said.

Onset-to-Door Times in Patients Treated With IV tPA

Onset-to-Door Times (min) n %
< 60 8111 64.7
61 – 180 4327 34.5
> 181 107 0.9

The frequency of delivery of tPA was 27.1% of the golden-hour patients vs 12.9% in the 1-to-3 hour patients (P < .0001).

However, those arriving earlier also had longer DTN times. Patients who arrived at the hospital within the first hour had a mean DTN time of 90.6 minutes, compared with 76.7 minutes for those arriving between 1 and 3 hours after symptom onset. Only 18.3% of these patients who arrived within 60 minutes of symptom onset had a DTN time under the recommended target of 60 minutes.

There was a "modest increase" of about 1.2% per year over time in the number of golden-hour patients being treated within 60 minutes, from 12.8% in 2003 to 19.5% in 2007; this improvement did not appear to be related to length of participation in the GWTG-S program, he noted.

Having More Time Should Not Mean Taking More Time

After his presentation, Dr. Saver was asked about what might explain the longer times to treatment among those who arrived earlier. Although they plan to look at this issue further in this data set, he pointed out that doctors might take the opportunity for a longer informed-consent process when they have more time.

Furthermore, during a press conference here, Dr. Saver speculated that this potential problem of using the time for deliberation may worsen over time, given the results of ECASS 3 reported last fall that showed thrombolytic therapy was safe and effective up to 4.5 hours after symptom onset.

"I think for the providers, focusing the attention on how well your health system is performing by focusing on door-to-needle time for treatment, rather than the onset-to-treatment time or the maximal permitted time, is the way to go," Dr. Saver said. "We're trying to emphasize a door-to-needle time of 60 minutes."

Arthur Pancioli, MD, professor and vice chair of emergency medicine at the University of Cincinnati, in Ohio, moderated a press conference here where this paper was presented. He pointed out that while there is a benefit to treatment, there are also serious risks associated with thrombolytic therapy, including a 6.4% risk of hemorrhage, "even if you're doing it right."

While it is still clearly the right thing to do, he said, "that would give you pause . . . but what you cannot do is pause, and that's the hard part.

"We're caught in a situation where you have to be fast, and you have to do it well."

The study was funded by the American Heart Association PRT Outcomes Research Center and the National Institutes of Health-National Institute of Neurological Disorders and Stroke. Dr. Saver reports he is an investigator in the NIH CLEAR, IMS-3, and MR-RESCUE trials.

International Stroke Conference 2009: Abstract 31. Presented February 18, 2009.

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