On the basis of reports published in September 2008 from two large international studies, professional stroke organizations extended the recommended time between symptom onset and administration of alteplase from 3 to 4.5 hours (JW Emerg Med Sep 24 2008 and JW Emerg Med Sep 15 2008). To assess implementation of the wider treatment window and its effects, investigators analyzed data for nearly 24,000 patients who were included in one of the study’s stroke registry from 2002 to 2010.

Overall, 2376 patients received alteplase between 3 and 4.5 hours after symptom onset; the proportion of patients who were treated within this window was three times higher in the last quarter of 2009 than in the first quarter of 2008. Rates of poor outcomes were low: 7.1% of patients treated within 3 hours and 7.4% of those treated at 3 to 4.5 hours had symptomatic intracerebral hemorrhage and 12.3% and 12.0%, respectively, died within 3 months. However, in analyses adjusted for confounding variables, patients treated at 3 to 4.5 hours had significantly higher rates of symptomatic intracerebral hemorrhage (1 extra hemorrhage for every 200 patients) and 3-month mortality (1 extra death for every 333 patients), as well as significantly worse functional outcomes (odds ratio for functional independence, 0.84). Median time from admission to treatment was 65 minutes before and after the reports. The authors conclude that the extended treatment window was implemented rapidly with no overall increase in admission-to-treatment time and that although risk from alteplase was greater when administered at 3 to 4.5 hours, treatment was still beneficial.

Comment: Although the U.S. FDA has not yet approved use of alteplase beyond 3 and up to 4.5 hours after onset of ischemic stroke symptoms, this evidence supports a wider treatment window and professional organizations recommend it. Nevertheless, time is brain, and eligible patients should be treated as soon as possible.

Published in Journal Watch Emergency Medicine August 27, 2010