Late application of clot-buster in stroke studied with MRI

International Stroke Conference Late-Breaking News:

NEW ORLEANS, Feb. 22 — Studies of a a clot-busting drug administered three to six hours after the start of ischemic stroke symptoms suggested that the agent can restore blood flow to the brain and improve clinical outcomes in some patients, according to late-breaking science trial results presented at the American Stroke Association’s International Stroke Conference 2008.

However, the study did not succeed in meeting its primary endpoint, which was showing that tPA could significantly reduce the growth in the area of the brain affected by the stroke as shown by magnetic resonance imaging (MRI).

      The clot-buster tissue plasminogen activator (tPA) – the only drug approved by the U.S. Food and Drug Administration for urgent treatment of strokes caused by blood clots – is approved for use only within three hours of stroke symptoms, and this study sought to assess the benefits and risks of extending that time period. 

      The Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) is the first randomized, double-blinded, placebo-controlled trial examining whether tPA could be administered safely and effectively more than three hours after an acute ischemic stroke in patients with potentially salvageable brain tissue as detected by magnetic resonance imaging (MRI).

      The study will be simultaneously published in Lancet Neurology.

Previous studies have shown that a subset of stroke patients, those with salvageable brain tissue called “perfusion-diffusion mismatch” on MRI, may experience enhanced blood flow and better clinical outcomes if treated with tPA.

Researchers at 15 centers in Australia, Belgium, New Zealand and Scotland screened 1,224 patients whose stroke symptoms had begun three to six hours earlier.  Of 101 randomized patients, mismatch was present in 86 percent.  Of those, 37 patients received tPA and 43 received a placebo saline solution.  Their average age was 71 and their average time-to-treatment was about five hours from stroke onset.

  “While the effect of late application of tPA on infarct growth – which was the primary outcome – was not significant, there was a strong trend toward infarct reduction,” said Stephen M. Davis, M.D. lead author of the study and professor of neurology at the University of Melbourne, Melbourne, Australia.

  In addition, tPA was associated with significant restoration of blood flow at three to five days and improved functional outcomes at 90 days. However, while Davis noted the study was too small to draw definitive conclusions on the effect of tPA, he suggested that the results provide support for further studies on extending the time window for tPA.

Grant funding was supplied by the National Health and Medical Research Council and the National Stroke Foundation, both of Australia, and the Heart Foundation of Australia. Boehinger Ingelheim supplied the drug (tPA or placebo), but was uninvolved in the study’s design, data management or analysis.

Author disclosures: PAION, Servier, Novo Nordisk advisory boards; Lectures for Boehringer Ingelheim, Sanofi Aventis, Pfizer, Novo Nordisk; No pharmaceutical stock holdings.

Statements and conclusions of abstract authors that are presented at American Heart Association/American Stroke Association scientific meetings are solely those of the abstract authors and do not necessarily reflect association policy or position.  The associations make no representation or warranty as to their accuracy or reliability.

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NR08-1023 (ISC08/LB1/Davis)