The Window of Opportunity Widens: Thrombectomy's Practice-Changing Implications in Stroke

Andrew N. Wilner, MD


January 23, 2019

This decade has seen the gradual acceptance of mechanical endovascular thrombectomy for treating acute stroke, an invasive procedure once considered to have little value in this indication. However, in the past year alone that acceptance turned to outright enthusiasm for many, with the high-profile DAWN[1] and DEFUSE 3[2] randomized controlled trials both noting that thrombectomy produces superior outcomes to standard treatment alone in certain patients, and recent guidelines[3] from the American Heart Association (AHA)/American Stroke Association (ASA) greatly extending the time range in which it can be performed.

Andrew N. Wilner, MD, spoke with Marc Malkoff, MD, a professor of neurology and vice chair of the neurology department at the University of Tennessee Health Science Center in Memphis, about how these recent results are reshaping what we think about the management of patients with acute stroke and the window of opportunity we have for making a difference in their prognosis.

A New Understanding of How, and When, We Can Intervene

Wilner: I went to a meeting a few years ago in which they presented thrombectomy cases, and it just seemed like a disaster. There were bleeding and complications, and the patients weren't any better as a result. It sounds like something has changed.

Malkoff: I think two things have changed. First, we're better at patient selection; second, the newer devices have a much higher technical success rate. That combination is what I think is giving people much better outcomes.

Wilner: What do these studies show us about the right time to use thrombectomy?

Malkoff: Thrombectomy is really designed for large vessel occlusions. There are multiple criteria, but when you boil it down, you perform thrombectomy when there is evidence of viable tissue in the distribution of the vessel occluded.

Although the DAWN and DEFUSE 3 trials are slightly different, they used various estimates of core infarction and penumbra, either based on MRI or CT criteria, to extend the window out to 24 hours. They were strikingly positive and also notable because they had a high rate of technically successful recanalization.

Wilner: What about intravenous tissue plasminogen activator (tPA)? Are we still going to use that?

Malkoff: Yes, because it appears that when you summarize all of the data in stroke, if you can recanalize non-dead tissue, the patient does better. So tPA does work, though it's not as potent or as reliable as thrombectomy.

The problem is that not every patient is going to be a thrombectomy candidate. Also, if you give tPA on top of that and then go on to thrombectomy, there is at least no evidence that the patients are worse off; some of them may be better off.

Then the other factor is that thrombectomy is a technique for large vessel occlusions which, depending on estimates, account for between approximately 15% and 25% of all strokes. Among that group, there will be a small percentage in whom you can't perform thrombectomy for technical reasons. And then there's also some fraction of cases in which the tissue will die before thrombectomy can be attempted.

So if you only do intra-arterial, you're going to be working on a very small fraction of overall strokes.

Wilner: What do the new AHA/ASA guidelines[3] recommend about the time range in which you can use thrombectomy?

Malkoff: The new guidelines allow you to go up to 24 hours. They recommend that you use a mixture of the DAWN and DEFUSE criteria. Again, these trials were similar but slightly different in exactly the way they applied. But basically, all the studies looked for patients who had relatively large volumes of tissue that they thought was ischemic but not dead—not core infarction.

Wilner: The DEFUSE 3 study results were really remarkable. That was a 6- to 16-hour range, and most of those patients did not get tPA, I guess because of the late treatment.

Malkoff: Yes, because of the time window. In the DAWN trial, which was up to 24 hours, a relatively small percentage may have gotten tPA. But it's mostly due to the fact that we found out that in some patients, the brain tissue doesn't die immediately. Basically, all of these studies are sort of different ways of trying to figure that out.

Who Benefits From Thrombectomy?

Wilner: Regarding the new understanding of how quickly brain tissue death occurs, is that because of the circle of Willis?

Malkoff: Part of it is, and probably part of it is due to collaterals. Certainly, most of the patients who did well seemed to have good collaterals.

There's an argument over what's the best way to pick out patients who really are going to benefit from this. Do you use a sort of perfusion scan looking at core infarction and penumbra either by MRI or CT? Do you use a collateral score? The two studies did some variant of the first mechanism, but it seemed that most of the patients had good collaterals.

The other thing that plays into this is the metabolic condition of the patient's brain, which is something we don't have a good way to measure or control for right now.

But it appears that the earlier dogma, that after 6 hours the brain tissue is dead, is not true. These studies are an elegant demonstration of that.

Wilner: From a practical point of view, it sounds like this is going to be something we're going to be doing more and more for about 15%-20% of stroke patients.

Malkoff: Well, the number of patients who are actually going to be eligible for this is probably closer to 2%-4%.

Wilner: Only 2%-4%?

Malkoff: Yes, that's the estimate of patients who would meet criteria for thrombectomy within the extended time window.

You have to realize that this is all large vessel occlusions. In roughly half of them, the stroke will be fixed or you're going to be way too late. And then of that fraction, you have to have the right anatomy, and then you're going to have to be in a stroke center.

What it means is that you're going to have to screen all stroke patients within 24 hours to get to that 2%-4%.

Where Should Patients Be Treated?

Wilner: That's a great segue into my next question. Who should be performing the thrombectomy?

Malkoff: It should be somebody with neurointerventional skills, whatever your base background is: stroke, neuro-critical care, neurosurgery, radiology. Those are the people who ideally should be doing this.

However, this is going to get murkier because the AHA/ASA has formed a Joint Commission certifying thrombectomy-capable stroke centers.[4] In that scenario, the criteria for doing these procedures is less well defined than maybe anybody that can put a catheter in you.

Wilner: I guess it reinforces the importance of stroke centers as a concept, where you have all of the pieces work well together and they are always available.

Malkoff: This is going to become a philosophical problem down the road, because many primary stroke centers do not have interventional capability. The debate will be, do you need to take all patients directly to the comprehensive center, or can you take them to the primary stroke center for their tPA and then transport?

At least locally, what we have found is that sometimes, to quote one of my colleagues, "The epoch of time to transport patients is biblical." This is going to be a problem, because if we'd go to the first route, comprehensive stroke centers generally don't have room to take care of every stroke patient. So you almost have to make an exception in order to manage the volume. If you go to the nearest primary stroke center and then delay transport for thrombectomy, you may still benefit some patients, but you're going to lose patients along the way with the time required.

This is going to become something that people who design stroke systems are going to have to grapple with, as well as the increased requirement for screening, because the number of patients to screen has gone up significantly.

Wilner: Overall, it's good news for people with stroke, and it sounds like a lot more work for everybody else to make sure the right patient gets the right treatment at the right time.

Dr Malkoff, I want to thank you for speaking with us today and sharing your insights and experience regarding the acute treatment of stroke with thrombectomy.

Malkoff: Thank you very much, Dr Wilner.

Follow Dr Andrew Wilner on Twitter: @drwilner


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