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Giving tPA to stroke patients within 6 hrs of symptom onset does not improve mortality or independence at 6 months.  However, patients might be a little “less disabled” while they are alive. Maybe.

Why It’s Important for Emergency Medicine

This is perhaps the most controversial article of 2012, call it thrombolytics-gate.  As the body of research on thrombolysis in acute stroke gets scrutinized closer, more and more ED physicians are questioning the purported benefits of tPA.  IST-3 is the biggest study of them all, enrolling over 3000 patients of all ages and stroke severities, but does little to clear up the confusion. See for yourself below…

Major Points

  • No difference in number of patients alive and independent @ 6 months
  • Patients who got tPA at < 3 hrs did well, between 3-4.5 hrs did worse, between 4.5-6 hrs did well again –  this randomness argues against time making a difference.
  • Secondary analysis suggests that though patients treated with tPA did not live longer or independently, they did survive with less disability.

Design & Results

  • Unblinded RCT, 3035 patients (age>80 years old = 53%)
  • 156 hospitals, 12 countries, 11 years


  • The evidence that treatment patients survived with less disability was found through ordinal analysis and statistical adjustment – whatever that means…
  • Only patients in whom the benefit of tPA was “uncertain” but “promising” were included.

Reviewed by V.Nguyen

MIA 2012 = Most Interesting Articles series of 2012

IST-3 collaborative, Sandercock P, Wardlaw J, et al. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet. 2012;379(9834):2352-2363. [PubMed]
Michelle Lin, MD
ALiEM Founder and CEO
Professor and Digital Innovation Lab Director
Department of Emergency Medicine
University of California, San Francisco
Michelle Lin, MD


Professor of Emerg Med at UCSF-Zuckerberg SF General. ALiEM Founder @aliemteam #PostitPearls at Bio:
Michelle Lin, MD