Prof. Adnan Siddiqui
Prof. Adnan Siddiqui

An interview with Prof. Adnan Siddiqui, MD, PhD, Professor of Neurosurgery and Radiology, University at Buffalo, about aspiration thrombectomy versus stent retriever thrombectomy as a first-line approach for large vessel occlusion strokes.

Interviewed by Dr. Robert Regenhardt, MD, PhD, Fellow, Massachusetts General Hospital. 

They will be discussing the article “Aspiration thrombectomy versus stent retriever thrombectomy as first-line approach for large vessel occlusion (COMPASS): a multicentre, randomised, open label, blinded outcome, non-inferiority trial,” published in The Lancet.

Dr. Regenhardt: The endovascular thrombectomy (EVT) trials from the last few years have revolutionized the approach to the treatment of acute stroke from large vessel occlusion (LVO). For most patients enrolled in these trials, stent retriever devices were used for EVT. Indeed, the current stroke guidelines specifically recommend the use of stent retrievers for EVT to treat eligible patients. Therefore, the robust, randomized COMPASS trial may lead to practice changes at many institutions, encouraging interventionalists to perform a direct aspiration first pass technique (ADAPT). Would you mind describing your approach and experience with ADAPT?

Prof. Siddiqui: At Buffalo, we were some of the original stenting for stroke trialists. Dr. [J] Mocco was part of that group, and he took that with him after he completed his fellowship at Buffalo. We realized the value of putting a stent across a clot, like cardiologists do for STEMIs. However, when you drop a stent into someone, you need to put them on aspirin and Plavix. And, unlike in the heart, most of the time there is no underlying plaque. The lesion causing the occlusion often is an embolus that traveled from somewhere else to the brain. As part of that original stenting for stroke trial, towards the end, we were using a stent called Enterprise. Enterprise came in a long size and you could actually partially deploy it and drag it back. Lo and behold, we would retrieve the stent and out came the clot. And so that was the genesis of the whole stent retriever concept, and that caught on like wildfire.

There was another stent for aneurysms at the time called Solitaire, which started being used for stroke. That was right around the time we were enrolling patients in IMS III, MR RESCUE, and SYNTHESIS, the negative trials of 2013. Those were still ongoing when we realized that compared to Merci and other devices, stent retrievers were infinitely better. This resulted in us starting the stent retriever versus best medical therapy trials, which resulted in the tsunami of positive trials in 2015. We were in the mindset of trying to see what would work and what would work better. One of the early iterations of stent retrieval was that you put a stent retriever in the head and guide catheter in the neck. It was quite scary pulling the stent retriever with clot all the way back down into the neck into the guide. We realized that if we had a large bore catheter in the head we could directly aspirate while pulling the stent retriever. It made life a lot simpler. The clot came out, and you didn’t have to deal with physical forces of guiding the stent all the way from the head to the neck.

Then, I think it was Dr. [Aquilla] Turk who, instead of pulling the stent retriever into the distal aspiration catheter, he just went up with the aspiration catheter alone, sucked on the clot, and the clot came out. These experiences were shared, and others had similar incredible outcomes. We could just suck the clot out and not have to open a stent retriever, which is a $6000 device. This was right around when we were finishing the 2015 stent retriever trials, so this predated all those positive results. We were doing aspiration already when the 2015 trials came out and the world changed. We were saying, “There is another way of doing this, too!” But many around us were saying, “No, the guidelines are clear and stent retrievers are the only way to do it.” That was the genesis of the COMPASS trial. We thought aspiration was just as good of a way to open vessels for acute stroke.

Dr. Regenhardt: In your opinion, what are the advantages of ADAPT over stent retriever EVT?

Prof. Siddiqui: There are a few advantages the way I look at it, at least the way I do it. I like to do aspiration first particularly when I get my aspiration catheter all the way up to the clot over a microcatheter and wire without having to cross the clot.

Let me explain why not crossing the clot is beneficial. When you take an LVO patient to the cath lab and do an angiogram, what you see is a cutoff. You can’t see beyond it. That is sort of scary because an individual’s vessel patterns, while they are stereotypical in some ways, are actually quite individual sort of like fingerprints. Even though everyone has an ICA and an MCA, the precise branching pattern is unique. When you are forced to go from what you can see to what you can’t see, as you do when passing a stent retriever through a clot, there is risk involved with that. There could be an aneurysm on the other side of the occlusion. The wire could go into a small branch or even go through a blood vessel. Indeed, some of these things do occur. With direct aspiration, I can go just proximal to the clot face and stay in the part of the vessel I can see. Without crossing the cutoff, I don’t have to go into the unknown.

The second thing I like is that if there is an underlying plaque like coronary vessels, which occurs in 1/10 cases, a stent retriever can injure the vessel as it is dragged through the ruptured plaque. It becomes almost an impossible situation where you need to stent them because you have ripped open a raw plaque. In contrast, with aspiration you can often see there is an underlying plaque, you don’t injure the vessel with a stent retriever, and you can use balloon angioplasty and avoid putting the patient on aspirin and Plavix.

The third advantage is the obvious cost savings. Aspiration catheters are typically $1500-2000, whereas stent retrievers are in the $5000-7000 range. With the aspiration catheter alone, if you get the job done, you saved the hospital some money.

Finally, if you first try aspiration and it doesn’t work, you have a large bore catheter there already with which you can easily go into the unknown with a stent retriever. You haven’t burned any bridges.

For all those reasons, I think it is really valuable to have aspiration validated as a technique for EVT, especially on the first pass.

Dr. Regenhardt: The COMPASS trial demonstrated ADAPT conferred a non-inferior functional outcome at 90 days compared with using stent retrievers as first-line. 134 patients were randomized to ADAPT and 136 to stent retriever first-line. A modified Rankin score of 0–2 at 90 days was achieved by 69 patients (52%; 95% CI 43·8–60·3) in the ADAPT group and 67 patients (50%; 41·6–57·4) in the stent retriever group (pnon-inferiority=0·0014). There were also no differences in recanalization rates or safety outcomes. How should interventionalists and other stroke clinicians modify their practice based on these data? In your opinion, is the question now settled? Should all interventionalists adopt ADAPT?

Prof. Siddiqui: No, actually quite to the contrary, I think that the thing to keep in mind is that these are equally good techniques. One of things that bothered me when the first guidelines came out after the 2015 trials was that instead of stating that EVT in general was the way to do it, they stated that stent retrieval was the standard of care. While stent retrieval was used for the majority of patients enrolled in those trials, it wasn’t the only technique. ESCAPE, for instance, had a significant number of people who used aspiration first as a methodology for EVT. The guidelines were not procedure-based, but tool-based. What we really wanted to accomplish with COMPASS was to establish that aspiration first was an equally valid technique. For those who prefer stent retrieval, they need to know that if it doesn’t work after 2-3 times, maybe they should try aspiration. And for others who want to use aspiration first, I think that is a perfectly legitimate first pass technique. That is really my message: There are multiple ways of opening blood vessels that are occluded in patients with acute ischemic stroke, and ADAPT is jut as valid as a stent retriever. 

Dr. Regenhardt: You were mentioning that the preference of the interventionalist is sometimes a factor in the decision for EVT approach. Are there any situations in which an interventionalist may still find first-line stent retriever EVT preferable? For instance, are certain vessel lesions better suited to one approach or the other?

Prof. Siddiqui: Great question. It is a different methodology the way I think about it. The first instance in which stent retrievers should be considered is when you cannot get your aspiration catheter all the way to the face of the clot. Catheters, while they are getting better, still cannot overcome the tortuosity in the brain vessels of all patients. This occurs not infrequently, when even the next generation aspiration catheters don’t quite get all the way up there. If that is the case, don’t just aspirate from wherever you are. Go across the lesion with a stent retriever and try to maximize the opportunity for the best outcome.

An instance where stent retrievers should be avoided is when the lesion involves the distal MCA branches. The M2 and M3 branches, particularly off the superior trunk, typically float along in the breeze in the sylvian fissure in the spinal fluid. If you put up a stent retriever and drag it back in these distal lesions without a very close aspiration catheter, you are liable to injure these tiny branches and there is a higher risk of hemorrhagic transformation. Perhaps a direct aspiration approach with smaller catheters may be preferred in some of these more distal, more fragile vessels. The evidence remains to be seen, but this is more of a feeling when you ask me the way I switch from one technique to the other based on where the lesion is.

Dr. Regenhardt: The COMPASS trial enrolled patients with anterior circulation (ICA, M1) LVO within 6 hours of onset and without large infarct cores on CT (ASPECTS ˃6). Do you think these results are generalizable to patients presenting after 6 hours if DAWN or DEFUSE 3 criteria are met? Should ADAPT also be considered for tandem lesions and posterior circulation LVO?

Prof. Siddiqui: While ADAPT was limited as far as the trial is concerned for patients with acute ischemic stroke up to 6 hours, it remains just as effective for patients who present well beyond the 6-hour mark and for those with posterior circulation LVOs and tandem lesions. I don’t think there is anything inherently higher risk with aspiration in these situations. Obviously, we don’t have a trial up to 24 hours yet, but I assure you those will be forthcoming. As newer devices come around, they want evidence to support efficacy for all lesions regardless of time point.

One particular problem with posterior circulation LVOs is that vertebral arteries are typically smaller than the internal carotid arteries. Therefore, you must go with a smaller system in these cases because you can’t use the large system without having a fairly large guide catheter. This poses a little bit of challenge, but it is routinely overcome.

As far as tandem lesions are concerned, aspiration works just as well, but you must work with the proximal lesion. What I prefer to do, and this is completely up for debate and I’m not sure at all I am right, is to stent the neck first. Once the stent is in the neck, I treat the distal lesion like I would any other. I try aspiration if I can get up to it, and if I can’t, I use a stent retriever with aspiration.

Dr. Regenhardt: The COMPASS trial requested interventionalists do 3 passes with the assigned approach, then allowed the use of any therapy thereafter for persistent occlusions. In your opinion, is this the preferred number of times to use aspiration before switching approaches in clinical practice?

Prof. Siddiqui: Great question. I am not sure. That is what the trial mandated. I certainly find, in my own practice, I will try aspiration once or twice, then I will incorporate a stent retriever into the tool kit. But just giving a technique one pass is a little hard to do in a clinical trial. Therefore, the trial mandated 3 passes with either approach before you could switch. In clinical practice, I typically do two passes, and if that is not working, I switch for the third. I think it is more about what you do on your very first pass. For the very first pass, aspiration really is an excellent technique if you can get to the clot face with the aspiration catheter. If you get to the clot with the aspiration catheter and you try it once with a poor result, I have no objection to people switching directly to stent retriever for pass number two.

Dr. Regenhardt: Also, is ADAPT best performed with a vacuum pump, or is manually aspirating with a large syringe also feasible?

Prof. Siddiqui: Again, this is an unsettled issue. I personally prefer a vacuum pump on the aspiration catheter and a syringe on the guide catheter. That is my preferred combination, but there are others who like a syringe on both. I am somewhat concerned that maybe my suction on the syringe might be stronger, more aggressive, and potentially harmful to a blood vessel compared to a pump. But, the honest answer is the biggest reason I like pumps is that it keeps my hands free to do other things.

Dr. Regenhardt: The COMPASS trial showed median time to TICI ≥2b was 11 minutes faster (p=0.0194) and median time to final recanalization was 10 minutes faster (p=0.0322) with ADAPT. What makes ADAPT faster?

Prof. Siddiqui: You just skip out on a couple of steps, which explains most of the time difference. As you can imagine, you just go up with the aspiration catheter and microcatheter, but you don’t have to cross the lesion. This means you don’t have to be tentative in terms of whether you are in the right vessel. You don’t have to do a microinjection to make sure you are in a good vessel beyond the clot. You don’t have to load the stent retriever, push the stent retriever, deploy the stent retriever, and leave it up there for 3-5 minutes. Most people wait at least 3 minutes if they don’t wait the full 5 minutes. Then you pull the stent retriever back. In the case of ADAPT, you skip all these steps. Instead, you just leave the aspiration catheter at the clot face for a couple minutes; most people don’t wait longer than 2 minutes. Then you just pull it back. This is where you can save 5-10 minutes.

Dr. Regenhardt: You mentioned cost a little already. One study showed a hospitalization cost saving per patient of nearly $20,000 with ADAPT (Turk et al, JNIS 2015 7(9):666-70). The COMPASS trial included a prespecified device cost analysis that showed ADAPT reduced cost per EVT by around $5,000. Another study estimated the annual incidence of LVO stroke to be up to nearly 78,000 in the U.S. (Rai et al. JNIS 2017 9(8):722-6). In a back-of-the-envelope calculation, if all interventionalists consider waiting to open a stent retriever and utilizing ADAPT, this could save the U.S. healthcare system up to $390 million annually in device costs alone. How can our system encourage more interventionalists to consider ADAPT?

Prof. Siddiqui: I think we are already getting there. We are in the process of evaluating all the procedure codes and devices people are using. There is a clear shift towards aspiration as a first pass technique. I have a hard time believing the whole hospitalization costs were $20,000 cheaper, as that would suggest there was some benefit to aspiration beyond that of stent retrieval. At least in our trial, we did not identify improved outcomes or reduced complications with ADAPT. These were equivalent, so from that standpoint, overall, I believe the true delta is the cost of stent retrievers. I think that is a significant message as more physicians are more in tune with the costs to do a procedure. I think the shift toward ADAPT is sort of organically spreading throughout the interventional community.

Dr. Regenhardt: That was fantastic. I appreciate the opportunity to hear your insights and the history about how this technique was developed. Thank you very much.

Prof. Siddiqui: My pleasure.