Risk for favorable outcomes decreases with increasing time to treatment from stroke onset, and, after 4.5 hours, alteplase treatment might increase mortality.
What is the optimal interval between stroke onset and intravenous recombinant tissue plasminogen activator (rt-PA) administration?
Researchers conducted an updated analysis of pooled data from eight trials involving 3670 patients (median age, 68; age range, 19–101) who were randomized to receive rt-PA or placebo within 360 minutes of onset of stroke symptoms.
In multivariate logistic regression analysis, the odds of a favorable 3-month outcome (based on modified Rankin scale score, Barthel index score, and National Institutes of Health Stroke Scale score) were inversely related to time from onset of symptoms to rt-PA treatment, with no treatment benefit after about 270 minutes. Adjusted odds of favorable 3-month outcomes were 2.55 for 0–90 minutes, 1.64 for 91–180 minutes, 1.34 for 181–270 minutes, and 1.22 for 271–360 minutes. Adjusted odds of mortality increased with time to treatment, ranging from 0.78 for 0–90 minutes to 1.49 for 271–360 minutes. Large parenchymal bleeds occurred in 5.2% of rt-PA patients versus 1% of controls and were independent of time-to-treatment interval. The authors conclude that time from stroke onset to treatment should be minimized and that after 4.5 hours, "risk might outweigh benefit." An editorialist adds that, in large middle cerebral artery infarcts, "20 million additional neurons die every 10 min[utes] if reperfusion is not achieved."
Comment:
In multivariate logistic regression analysis, the odds of a favorable 3-month outcome (based on modified Rankin scale score, Barthel index score, and National Institutes of Health Stroke Scale score) were inversely related to time from onset of symptoms to rt-PA treatment, with no treatment benefit after about 270 minutes. Adjusted odds of favorable 3-month outcomes were 2.55 for 0–90 minutes, 1.64 for 91–180 minutes, 1.34 for 181–270 minutes, and 1.22 for 271–360 minutes. Adjusted odds of mortality increased with time to treatment, ranging from 0.78 for 0–90 minutes to 1.49 for 271–360 minutes. Large parenchymal bleeds occurred in 5.2% of rt-PA patients versus 1% of controls and were independent of time-to-treatment interval. The authors conclude that time from stroke onset to treatment should be minimized and that after 4.5 hours, "risk might outweigh benefit." An editorialist adds that, in large middle cerebral artery infarcts, "20 million additional neurons die every 10 min[utes] if reperfusion is not achieved."
Comment:
These data suggest that the risk for favorable outcomes decreases by a factor of about two for every 90-minute delay in treatment from stroke onset and that after 4.5 hours, rt-PA treatment might increase mortality. Lytic therapy for acute stroke must be given at the earliest possible time. Extension of the window for treatment to 4.5 hours is not a license for delay; every minute counts.
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Kristi L. Koenig, MD, FACEP
Published in Journal Watch Emergency Medicine May 28, 2010
Citation(s):
Lees KR et al. Time to treatment with intravenous alteplase and outcome in stroke: An updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010 May 15; 375:1695.
Saver JL and Levine SR. Alteplase for ischaemic stroke — Much sooner is much better. Lancet 2010 May 15; 375:1667.
Published in Journal Watch Emergency Medicine May 28, 2010
Citation(s):
Lees KR et al. Time to treatment with intravenous alteplase and outcome in stroke: An updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 2010 May 15; 375:1695.
Saver JL and Levine SR. Alteplase for ischaemic stroke — Much sooner is much better. Lancet 2010 May 15; 375:1667.
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