AAN 2009: New Studies Offer Important Insights on Stroke Treatment

Mark J. Alberts, MD; Lawrence R. Wechsler, MD


May 20, 2009

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Mark Alberts, MD: Hello. My name is Dr. Mark Alberts. I'm professor of neurology and director of the stroke program at Northwestern University in Chicago. I'm here with my colleague.

Lawrence Wechsler, MD: I'm Dr. Lawrence Wechsler. I'm the director of the UPMC Stroke Institute at the University of Pittsburgh.

Dr. Alberts: We're here at the American Academy of Neurology meeting in Seattle, Washington, to bring you a Medscape WebMD blog update about new studies related to stroke that are being presented at this meeting.

The first study I would like to share with you is a meta-analysis of 20 studies that looked at over 2500 patients who had symptomatic carotid artery disease.[1] This meta-analysis looked at the efficacy and safety of ECIC [extracranial-intracranial] bypass vs best medical therapy in all of these studies.

What they found is that there was no evidence of benefit for surgery compared to best medical therapy across all of these studies for the endpoints of death, death and dependency, or stroke. I liked this because it was one of the largest meta-analyses that's ever been done looking at the safety and efficacy of ECIC bypass vs best medical therapy. Larry?

Dr. Wechsler: Mark, this is a procedure that's been around a long time and at one time was performed quite a bit by many surgeons who spent many years training to do this procedure. It has largely gone out of fashion for the reasons that this study has kind of outlined because the benefit of it has really never been able to be shown, as this meta-analysis has confirmed.

But there are still some question as to whether there might be some benefit in selected individuals who have appropriate physiology in the brain from which they would benefit from a procedure like this. Those would be people who have blockage in an artery and have an area of the brain that is starved for the circulation, and that by doing this bypass to restore the circulation, they can indeed be benefited. But it's probably a small group of patients and it's difficult to find in these large studies, and particularly in a meta-analysis.

Dr. Alberts: I agree. In fact, I think there's an ongoing study looking at those subgroups of patients.

There was another interesting study done in Canada, where they looked at 13 different stroke centers that were seeing acute stroke patients.[2] This study looked at 1400 patients seen at these 13 different stroke centers and correlated the time delay between stroke onset and when the patients went to the emergency department [ED], with the time delay in terms of once they hit the ED, how long it took them to actually received tPA [tissue plasminogen activator].

This was a very interesting study because they found that there was an inverse relationship. In other words, the sooner patients arrived at the ED after stroke onset, the longer they had to wait in the ED until they received tPA. The door-to-needle time was longest in those patients who got to the ED the quickest, and the door-to-needle time was the shortest in those people who took the longest time to get to the ED. It was almost like the physicians and other medical people in the ED, not that they were dragging their feet, but they didn't seem to be in that much of a hurry to treat these patients as soon as possible once they knew that they had maybe an extra few minutes or maybe even an extra hour to get into that 3-hour time window.

Frankly, this is a disturbing trend because we know that all of the studies show that, when it comes to tPA therapy, the sooner you can treat patients within 3 hours, the better the outcomes will be. We hope that we don't fall into this same trap going forward. Larry, do you have any thoughts about that?

Dr. Wechsler: I think this is an interesting observation because I think it shows kind of the downside of this concept of a window. We think of a 3-hour window for treating patients with IV [intravenous] tPA, but as Mark has pointed out, the earlier that we treat someone, even within that window, the better their chance of recovering from their stroke as a result of the tPA. But because we have this concept of a window at 3 hours, there's the idea that if someone comes in at 1 hour, that's great because now we have 2 hours to get the treatment in. Instead, people need to be thinking that, no matter what time the person comes to the emergency room, the sooner that treatment can be instituted, the better their chance for a good outcome and forget about the 3-hour or 4 and a half-hour window because it just tends to psychologically allow people to wait and relax because they think they have plenty of time for treatment.

Dr. Alberts: It's a very good point, Larry. Speaking of tPA in stroke centers, there are a few presentations at this meeting talking about primary stroke centers and the use of tPA in those stroke centers. Larry, I know you reviewed those. Do you have any comments?

Dr. Wechsler: Yes There are a couple of very interesting presentations, both of which are being made by my colleague here, Dr. Alberts. One of them is looking at the stroke centers that are certified by the Joint Commission.[3] The Joint Commission in 2003 started certifying primary stroke centers. This has been a very important advance in terms of increasing the utilization of IV tPA across the country. This particular study looked at the appropriate use of tPA in the stroke centers as a function of whether the stroke centers were certified by the Joint Commission once, twice, or in some cases, even 3 times now. The certification is a 2-year process, so every 2 years the stroke centers have to be recertified.

What Dr. Alberts found was that, as centers [become] recertified and go on in time, they have an even better track record in terms of appropriate treatment of patients with IV tPA. That is, the percent of patients who arrive in their emergency room who are eligible for IV tPA and in fact get treated gets higher with the first recertification, with the second recertification, even higher with the third recertification.

I think this shows that this process works, that there is a bit of a learning curve even within primary stroke centers, but that as people get more experience as primary stroke centers, they do better in terms of appropriate treatment of patients with tPA. Mark?

Dr. Alberts: Very good. The last study I would like to talk about was a small study that looked at treating patients who come in with a stroke due to cocaine, to see if they respond to tPA.[4] This looked at a relatively small number of patients, 7 patients with acute strokes presumed related to the use of cocaine. These patients were all treated with intravenous tPA.

What the study found is that, in general, the tPA was safe, it was well tolerated, there was no evidence of bleeding complications related to use of tPA in these cocaine-associated strokes. Interestingly enough, after workup, it was found that 5 of these 7 patients were presumed to have strokes from a cardioembolic etiology, not necessarily a cocaine-induced vasculitis. Oftentimes, in a busy ED setting, we don't know that the stroke is due to cocaine because sometimes the toxicology screen has not come back. But it's reassuring to know that we can still use tPA in this population of patients, and it appears to be safe. Larry, any thoughts on that?

Dr. Wechsler: I agree with what you've said, that this is a difficult group of patients and one in which we often wonder whether we are doing the right thing in treating them with IV tPA. This is certainly reassuring that these people will benefit and that this is an appropriate use of this treatment.

Dr. Alberts: Let me thank my colleague, Dr. Wechsler, and thank all of you for watching this Medscape Stroke Blog update. Thank you very much.


1. Lyrer PA, Fluri F, Engelter ST. Extracranial-intracranial arterial bypass surgery for occlusive carotideal cerebrovascular disease -- a systematic metaanalysis. Program and abstracts of the American Academy of Neurology 61st Annual Meeting; April 25-May 2, 2009; Seattle, Washington. P01.152.

2. Izenberg A, Silver F, Hill M. Earlier hospital arrival in acute stroke is associated with delayed tPA administration. Program and abstracts of the American Academy of Neurology 61st Annual Meeting; April 25-May 2, 2009; Seattle, Washington. S04.006.

3. Alberts MJ, Range J, Ann Watt A, et al. Impact of Joint Commission certification of primary stroke centers on the administration rate of IV tissue plasminogen activator for ischemic stroke. Program and abstracts of the American Academy of Neurology 61st Annual Meeting; April 25-May 2, 2009; Seattle, Washington. S04.002.

4. Ramos A, Doral FL, Reyes-Iglesias Y, et al. Intravenous thrombolysis in cocaine associated ischemic stroke. Program and abstracts of the American Academy of Neurology 61st Annual Meeting; April 25-May 2, 2009; Seattle, Washington. P03.156.


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