The tPA controversy

As you all may be aware, there is a fair amount of controversy surrounding the use of tPA in acute ischemic stroke. This becomes even more apparent when you talk about extending the “stroke window” to 4.5 hours. Rather than give you my personal opinion on this topic, I want to give you all a list of resources so that you can be well-informed and make your own decision. To do this properly will take some time on your part, but I promise you that this issue is not going away anytime soon. You need to fully understand this medicine so that if you give it to a patient and they die of an intracranial hemorrhage, you still feel that you did what was best for that patient at that time. Below are some recommended things to check out, including stuff that has been released in the past month.

1. Podcasts. There are several extremely high quality podcasts on the topic. If you want the quicker one (55 minutes), check out “Acute Ischemic Stroke” from the Oct 14, 2013 podcast of ERCast. Very good, but an overview. If you really really want all of the details and want to fully understand this topic, check out the June 28, 2012 episode of SMARTEM entitled “Thrombolytics for Acute Stroke” (2h, 35 min) and the August 12, 2013 update entitled “Thrombolytics for Stroke: Update” (1h, 23 min). I have listened to both of these twice because the information is so important, and they make the discussions fun.

2. You can always read the original articles and interpret the findings for yourself. The show notes for the above podcasts list the articles. Here is a link to the classic NEJM articles (about the NINDS studies): NEJM article
Of all of the tPA studies to know, NINDS may be the most important because it was the basis for the recommendations to give tPA to our patients. You should know about this study, and it is very helpful to look at the “Letters to the Editor” (you can click directly to these from the article) and see why a number of smart people didn’t like the study. They actually had to do 2 NINDS studies because NINDS-1 (looking at 24 hour outcomes) did not show any benefit to tPA. For those of you thinking, “I gave a patient tPA and they were much better 2 hours later”, it’s probably because you tPA’ed a TIA. Very interesting stuff.

3. Check out the March, 2015 edition of ACEP Now (it’s that monthly newsletter that we all get and occasionally read). Here is the link. Essentially, the clinical guidelines recommending tPA are changing. They used to be level A recommendations and there was such outrage that they are changing to level B. Below is a screenshot from the cover of the newsletter.


4. This is not a recommendation of something to read, but I wanted to share with you an item I received in the mail within the past month. It is pictured below and appears to be an update on stroke management. Look at the company that sponsored it (I zoomed in on it in the second picture). Guess what drug Genentech manufactures? Thought this was interesting as Genentech has their hands in a lot of the “research” that is being done on tPA and I felt this was particularly egregious to send something that looks like it might be legit (and you get CME for reading the article!) that is full of biased tables and charts (I can show it to anyone that’s interested).

Ok, that’s it for now. Just wanted you all to be aware of this current debate and to form an opinion on the matter. Ask your attendings how they feel about it. You’ll get wildly different answers from different attendings (trust me, I’ve already asked), and people tend to feel pretty strongly one way or another because the topic is so polarizing. Please post your thoughts and comments below!! And no, I’m not completely anti-tPA, I just personally don’t feel that we have narrowed down which patients will benefit and which won’t, and to give it to everyone indiscriminately seems not right to me…

3 thoughts on “The tPA controversy

  1. Anne told me I need to join the conversation.
    So, in bullet points.
    !) if you have no downstream flow everything dies that is not in a water shed area.
    2) tPA ia a bit of a plumbers mentality but it is a start
    3) tPA was supposed to be the beginning of a therapy not the end, in that we need to come up with methods to decrease the reperfusion damage, we are not there but will get there.
    4) what do you have better to offer these patents
    5) selection is the key and post stoke care cannot be underestimated
    6) remember mortality was the same in 2 groups and to Mark’s pony there was no difference at 24 hours between the 2 groups.
    7) door to drug time has become a national metric so it will not go away
    8) we need to be more wavy with the criteria and the mimics

  2. Thanks for the awesome commentary, Mark. These are all great points to keep in mind, especially regarding our neurologists, who are more than happy to make the call regarding tPA vs no tPA…this is definitely not the norm everywhere.

    Another interesting point regarding fibrinolytics (either the internal system or IV tPA) has to do with the composition of the “clot” that is causing the stroke. This isn’t my idea, it’s stolen from SMARTEM podcast, but I had never thought about it before. Thrombolytics seem to make sense in MI or massive PE because they lyse a clot (obviously). But if the patient is having a stroke because some old nasty piece of junk broke off from their carotid artery, is that the same as a clot? Will thrombolytics work in this case? Not sure if we know the answer to this one, but it seems like maybe the mechanism in stroke is different than the mechanism seen in most MIs, which is maybe why the data regarding efficacy of tPA in stroke is conflicting.

  3. Great topic. Anne brings up a critically important point in the middle of the post…that being that when you give a pt IV t-PA and they “magically get better in front of your eyes”, it is truly impossible to state with any certainty that this happened b/c of the intervention. It may have, it may not have, but if you understand the natural history of stroke/TIA you’ll know that some pts presenting with stroke syndromes have a spontaneous recovery, and this is b/c the body has this wonderful thing called the intrinsic fibrinolytic system, and if it can do it’s thing, and cardiac output is not compromised, then you can see pts have complete resolution of their strokes right in front of your eyes. Some of these are TIA’s, some are actually strokes.

    The definition of TIA is changing, and experts on the topic now use 1h as the definition for TIA. Two reasons for this 1) nearly all pts who have stroke symptoms for >1h have lesions on diffusion weighted MR, and recall part of the definition of TIA is “normal neuro imaging”, and 2) once your symptoms have been present for >1h your chances of spontaneous resolution fall precipitously.

    Here’s a link to an article by my residency program director (a noted t-PA zealot and part of the original NINDS trials) on the new definition of TIA. (

    For anecdotal evidence ask Inger about a case we had on tuesday where this very thing happened. NIHSS 20, dense MCA territory infarct based on his symptoms, sent to CT, t-PA cooking, and when he returns from CT he is completely normal. NIHSS 0.

    Realize that you are training in an institution where the ED has a somewhat anti-tPA for stroke bias. This is not wrong, nor is it right, it’s just reality. We also have a stroke team that is willing to make t-PA decisions on all these pts, thus displacing a lot of the burden of decision making. This is not the norm. Most of you will work in a community setting where you’re it…whether or not the pt receives any therapy for their ischemic stroke in the ED will depend entirely on you.

    Be informed observers…


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