An Important Update on Thrombolysis in Acute Stroke

July 02, 2012

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Hello, and welcome to this Medscape stroke update. My name is Dr. Mark Alberts, from Northwestern University in Chicago. Today, I want to update you about the results of the IST-3 (International Stroke Trial-3), the results of which were presented at the European Stroke Conference in Lisbon in May 2012, and also published in The Lancet at the end of May.[1,2]

This study was originally designed to be a 6000-patient study but enrolled only about 3000 participants. The goal was to look at the safety and efficacy of intravenous (IV) tPA (tissue plasminogen activator) administered within a 3-hour treatment window in patients with acute ischemic stroke. Patients were enrolled in the study only if investigators were unsure that the patient would or would not benefit from receiving IV tPA therapy. This is a little different from our usual intention-to-treat analysis.

The primary 6-month outcome was an Oxford Handicap Scale score of 0 to 2, and the secondary outcome was an Oxford Handicap Scale score of 0 to 1. At the end of 6 months, the study showed no statistically significant difference between the IV tPA group and the placebo group in the primary outcome. However, when they looked at the secondary outcome, they did find evidence of benefit for patients who received IV tPA.

What about other outcomes? Symptomatic hemorrhage occurred in 7% of patients treated with IV tPA vs 1% of the placebo group. Number of deaths at 7 days was higher in the tPA group than the placebo group, but all deaths at 6 months were about the same.

What about different time windows? The patients treated 0-3 hours after onset did better with tPA and the group treated 3-4.5 hours after onset tended not to benefit from tPA, but the groups treated 4.5-6 hours after onset did tend to benefit from tPA. The problem is that the confidence intervals for all 3 time groups tended to overlap.

What do we have at the end of the day with IST-3? It provides us with some inkling that tPA may be beneficial up to a 6-hour time window, but the data are hard to interpret. The outcome score -- which was not the modified ranking at 3 months that is used in many of the other studies, but rather is the Oxford Handicap Scale score at 6 months -- is somewhat atypical, and it is difficult to know how that compares with other rankings in other studies. The time window results showing some benefit at 3 hours and 6 hours, but not at 4.5 hours, are equally problematic.

Could this be a potential new therapy? The answer is yes. Is IST-3 definitive? I really do not think it is at the end of the day. I know that many of our European colleagues think that it is definitive, but I encourage you all to read the study for yourselves in The Lancet and see what conclusions you arrive at.

Thank you very much for attending this Medscape stroke update.


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