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Thrombolysis for Acute Stroke

Thrombolysis for Acute Stroke

As you know, the BEEM Team of Drs. Crocco, Milne and Upadhye was in Sweden last month for SweetBEEM. This was one of the best BEEM trips ever for a variety of reasons.

Members of BEEM were asked to speak at their National Emergency Medicine conference while in Stockholm. I was invited to debate the evidence for thrombolysis in acute CVA with Dr. Kjell Asplund. Being Canadian, it was more of a discussion on the topic rather than a debate. Here is an outline of what was covered in my presentation:

  • Null Hypothesis and Skepticism
  • Thrombolysis for Acute CVA
  • 12 Major RCTs
  • Community Setting
  • Systematic Reviews
  • Conclusion

I approached this challenge as a scientist who has been doing research for over 30 years. It started with the null hypothesis that the tPA has no overall benefit. The burden of proof was upon Dr. Asplund who was making the positive claim.

I presented the twelve major randomized control trials. There were four trials stopped due to harm or futility, six showing no difference, and only two showing benefit. This was not enough proof for me to reject the null hypothesis. None of the arguments were directly addressed by Dr. Asplund. It was up to the audience to decide what to make of the information presented. Thank you to Dr. David Newman and his great website the NNT which helped prepare this table.

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The different hierarchy of evidence was discussed briefly. This was followed by three observational studies of thrombolysis for acute stroke in the community setting.

The hypothesis that time is brain was questioned with two review articles. One was from Dr. Jerome Hoffman who is a very vocal skeptic of this therapeutic intervention. The other study presented was a Cochrane Systematic Review by Dr. Wardlaw. In this review it is stated: “the available data do not provide sufficient evidence to determine the magnitude of treatment effect, the duration of the therapeutic time window, the optimum agent (or dose or route of administration) ”

Another Cochrane Systematic Review by Dr. Wardlaw in 2013 questioned whether the type or does of lytic used made any difference: “the evidence is inadequate to conclude whether lower doses of thrombolytic agents are more effective than higher doses, or whether one agent is better than another”. 

Here is a copy of my slides from the presentation TPA in CVA pdf. You can also watch the 30 minute presentation on YouTube. I will upload Dr. Asplund’s presentation next week for everyone to review.

The conclusion from my presentation on thrombolysis for acute CVA was this meme.

Screen Shot 2014-04-08 at 2.57.04 PM

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

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  • StevenRobert

    Critical review of studies of TPA, or thrombolysis, don’t indicate that thrombolysis is effective at reducing the effect of stroke and possibly causes harm through intracerebral hemorrhage as well.
    There seems to be another school of thought in which data from a number of studies was pooled and the results seemed to turn out better, however there is criticism of the pooled data in that it was taken from heterogeneous studies, or there was differing base data and pooling such heterogeneous data does not result in a statistically reliable outcome.
    IN the US, the situation is clouded by widespread adoption of TPA for treatment of acute stroke, which appears to have made its use the standard of care, regardless of the question of statistically reliable outcome and since the TPA is in widespread use and widespread use has become the standard of care, physicians risk malpractice claims if TPA is not utilized in acute stroke management.
    That seems to be the situation we are in now.
    The other issue which has come up is that intravascular intervention with clot retrieval appears to be giving superior results even to TPA, so is use of TPA justified if intravascular intervention can be utilized, since it may have better outcome with less risk in experienced hands.