Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

The Debate on tPA for Ischemic Stroke at EMCrit – What Does the Research Really Say?

It puts the tPA in the patient, or else it gets the hose, again!

Should we look only at the so-called positive studies?

The proponents of tPA (Alteplase) are not trying to defend the other studies. They have a hard enough time putting a positive spin on the studies they want us to look at – just not too closely.[1]

Dr. Scott Weingart decided to bring two doctors together to discuss the problems with the research and whether those problems can be rationalized away (Not his description). I do not have the possibility of giving, or withholding tPA, so I do not have to worry about being punished for violating clinical policies – at least not when it comes to tPA. 😉

The debate seemed relevant because ACEP, a major US emergency medicine organization, released clinical guidelines markedly increasing stress on thrombolysing stroke. These clinical guidelines were sent back by ACEP’s council for further commentary and assessment, a move unprecedented in the history of the organization.[2]


Dr. Andy Jagoda presents the pro argument.

The research is not really that bad, just don’t suggest that the studies should be repeated with proper research methodology, because it would be improper to withhold the standard of care.

Organizations have looked at the research and made this a recommendation, so you have to justify not giving tPA, or you face punishment.


Bad standards of care are still bad medicine.

A decision not to use Alteplase in the appropriate setting is acceptable but clinical decision making must be well supported in the medical record[2]


Allow me to put that in perspective.

A decision not to use Alteplase in the appropriate setting is acceptable expected but clinical decision making must be well supported is taken for granted in the medical record.

Should any treatment be given without justification?

This is probably the biggest problem with medicine.

All treatment should require justification, every time.

Should treatment be justified with flawed research?

Dr. Anand Swaminathan gave the con argument.


The research is flawed.

The failure of the recommending organizations to identify these flaws does not mean that the flaws do not exist or that the flaws are insignificant.

IST-3 time to treatment randomization and outcomes.[3]

What is the magic that causes a good outcome when tPA is given at 0-3 hours, a reversal to a bad outcome at 3-4 1/2 hours, and another reversal back to a good outcome at over 4 1/2 hours?

The longer we wait, the more effective it is?

Isn’t this just a variation on the nonsense of homeopathy? The less we give, the greater the effect.

Here is the detail of the effect of time on outcomes, when giving tPA.

IST-3 time to treatment randomization and outcomes detail with my edits for clarity.[3]


A decision not to use Alteplase Magic™ in the appropriate setting is acceptable but clinical decision making must be well supported in the medical record.

Go watch/listen to the debate.

Also view the pro and con slides and read the detailed review of tPA for acute ischemic stroke at EM Lyceum[4] and Dr. David Newman’s much shorter review of the guideline problems at Smart EM.[5]


[1] The raw data of the NINDS trial should be made public
Dr. Jeffrey Mann
Rapid response letter

Unfortunately, it has been years since Dr. Mann discontinued his EM Guidemaps site, where he posted the raw data that the NINDS investigators finally sent him in 2003 (8 years after the study was published), and I no longer have a copy of what he posted.

Researchers should not keep their data secret.

[2] Podcast 116 – the tPA for Ischemic Stroke Debate
January 28, 2014
Dr. Andy Jagoda (pro) vs. Dr. Anand Swaminathan (con).
Podcast/Videocast page with links to the slides used by both doctors.

[3] 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.
IST-3 collaborative group, Sandercock P, Wardlaw JM, Lindley RI, Dennis M, Cohen G, Murray G, Innes K, Venables G, Czlonkowska A, Kobayashi A, Ricci S, Murray V, Berge E, Slot KB, Hankey GJ, Correia M, Peeters A, Matz K, Lyrer P, Gubitz G, Phillips SJ, Arauz A.
Lancet. 2012 Jun 23;379(9834):2352-63. doi: 10.1016/S0140-6736(12)60768-5. Epub 2012 May 23. Erratum in: Lancet. 2012 Aug 25;380(9843):730.
PMID: 22632908 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.

[4] tPA in ischemic stroke, “answers”
Posted on August 30, 2013
EM Lyceum

[5] The Guideline, The Science, and The Gap
Wednesday, April 17, 2013
Dr. David Newman browngorilla540
Smart EM