Given the procedure’s long-proven effectiveness, present-day advances in stroke thrombectomy treatments tend to be relatively incremental. That said, Jan Gralla (University Hospital of Bern, Bern, Switzerland) recently sat down with NeuroNews to discuss the latest hot topics within interventional stroke care—including a handful of ongoing developments that he feels could yet move the needle in this space.
While debates pitting the two prevailing thrombectomy device types—aspiration catheters and stent retrievers (SRs)—against one another have now raged on for almost a decade, high-level data remain quite sparse, and Gralla posits that such discussions are often a case of “beliefs rather than knowledge”. He states that meta-analysis findings indicate potentially improved outcomes with aspiration in very specific cases like basilar artery occlusions but, overall, “no one has proven a clear superiority, in any direction”, with one technique or the other.
It is worth noting, however, that the nature of these debates has shifted somewhat over that 10-year period since thrombectomy’s effectiveness was established in large vessel occlusion (LVO) strokes. Gralla highlights the fact that, initially, the standard thrombectomy procedure involved a balloon guide catheter (BGC), a microcatheter and an SR, with aspiration increasingly being incorporated into this paradigm over time.
“A lot of the time, we will skip the BGC, or at least use an additional aspiration catheter,” he explains. “So, very often, it’s SR plus local aspiration; you use your SR to get the aspiration catheter up, you partially bring the thrombus into the aspiration catheter with your SR, and then you pull everything out [via the ‘pinning technique’].”
This coupled with the growth in popularity of aspiration-only techniques means that, nowadays, the majority of device-related debates actually contrast usage of an SR alongside local aspiration against direct, contact aspiration without an SR.
“All of the developments we see in aspiration catheters therefore benefit SRs as well, which is important,” Gralla says.
Outlining possible advantages of the combined approach involving an SR, he highlights the fact that outcomes are generally agnostic to occlusion burden, making it a “very versatile, patient-independent” technique for almost every ischaemic stroke case, including those caused by very large thrombi.
“[Direct] aspiration is appealing because it’s cheaper, faster, and—for certain locations, anatomies and thrombus sizes—very successful,” he continues, noting that smaller or ‘floating’ thrombi, as well as occlusions in more distal vessels, are among those believed by many to be more amenable to this approach.
“So, from my point of view, if you want to be on the safe side, through day and night, and if you don’t have a lot of information on the thrombus, an SR plus a large aspiration catheter is great, because you can get a second tool in there and you will often have a very high recanalisation rate,” Gralla says. “But, for certain anatomical settings, aspiration appears to be equal and, in certain instances, may even be superior.”
Technical developments
The broad equivalence in clinical outcomes between SR and non-SR strategies—as well as the fact that SRs were the devices primarily evaluated in the multiple trials that established thrombectomy’s effectiveness 10 years ago—means they remain a key tool in the armamentarium of any physician performing interventional stroke treatments.
Nonetheless, even a cursory look at the areas currently being focused on by many companies in the neurovascular space suggests that the advancement of aspiration catheter technologies is of far greater interest.
“Technical development is much more intense on the aspiration side right now,” Gralla notes. “SRs are as they are; to my knowledge, no one is coming up with anything extraordinarily different here. The only things that have come up are the [adjunctive] use of aspiration catheters, which is now widely available and widely used, and the double-SR technique, which is a good option in certain settings and as a bailout technique, but tricky to advocate as a first-line treatment, because it significantly increases the financial expense, takes more time and—in many cases—won’t be needed.
“But, in aspiration catheters and aspiration in general, there are a lot of dynamics. We have the large-bore (e.g. 0.088-inch) catheters, and those trials seem to be running well. The tricky part, traditionally, has been bringing them up [into the neurovasculature] but, as of the past couple of years, the manufacturing quality has been so high and some newer catheters and adjunctive devices appear able to overcome the ledge effect of the ophthalmic artery, making it more feasible.”
In Gralla’s view, however, the single most promising and potentially impactful innovation in the thrombectomy space right now is the phenomenon of cyclic, or ‘pulsed’—as opposed to continuous—aspiration. While this is currently in an earlier stage of development compared to many other areas, Gralla’s initial impression is that it could “truly be a gamechanger” in the space.
“I’d say it has the highest potential,” he says. “I’ve been involved in benchtop testing and preclinical models, and it’s quite astonishing. If those findings hold true in a clinical setting, in terms of thrombus consistency and so on, it will make a real difference.”
It is believed that fluctuating aspiration forces over time creates an increased chance of ‘fatiguing’ the internal structure of a stroke-causing thrombus, leading to a higher likelihood of it being successfully—and completely—ingested by the catheter. Gralla predicts that, if this early promise can be replicated in human patients, the majority of thrombectomies will likely involve a cyclic approach within the next five years, owing to its potential to decrease emboli-related complication rates while also enabling more complete recanalisation by reversing flow and preventing distal embolism.
“We have very low complication rates with thrombectomy today, but one of the worst complications is embolising into different, previously unaffected territories,” he avers. “If cyclic aspiration is able to incorporate thrombi of various lengths and mechanical properties within the catheter before retrieval, these risks should be minimised. To shift thrombectomies completely into the location of the occlusion, instead of grabbing the thrombus and pulling it out, as with SRs or current aspiration techniques, is pretty much the holy grail.”
And, yet, while large-bore catheters and cyclic aspiration represent the most noteworthy innovations in thrombectomy devices right now, Gralla feels that simply combining the two may not actually be favourable.
“You might need to have some residual lumen in the vessel to apply cyclic aspiration,” he explains. “We may need to start going back to the ‘normal-sized’ aspiration catheters to achieve those pressure gradients. But, from my point of view, if there’s something extraordinary on the horizon after all these years of incremental developments, then it’s cyclic aspiration, for sure.”
The MeVO problem
A wide variety of factors have been cited as possible reasons for three randomised controlled trials (RCTs) evaluating thrombectomy in medium-vessel occlusion (MeVO) stroke—presented earlier this year—ultimately failing to demonstrate an overall benefit with the procedure. These factors include everything from the specific occlusion types that were included to the utilisation of thrombolytic drugs, to the timing of treatment and even patients’ baseline disability rates.
Variations between the different devices and procedural techniques that were selected across the DISTAL, ESCAPE-MeVO and DISCOUNT trials have also been pointed to by commentators, with some positing that aspiration-first approaches may produce improved outcomes versus SRs in more distally located occlusions. However, as stated in an editorial from Reade De Leacy (Mount Sinai Health System, New York City, USA) et al in Stroke: Vascular and Interventional Neurology, robust clinical data proving one technique’s superiority over the other are limited, with many analyses indicating comparable results between the two.
Gralla is largely in agreement with this view—aspiration-only approaches appear inherently safer compared to those involving SRs in more distal locations due to less force being exerted on vessel walls, but definitive evidence on whether or not this leads to a meaningful difference in patient outcomes is lacking.
In addition, Gralla notes that, while updates may be made to the available sizes and more granular characteristics of aspiration and SR devices, “no one is going to reinvent the wheel” when it comes to MeVO thrombectomy. He goes on to argue that adequate, appropriate tools were available from the beginning of those three randomised trials, instead highlighting patient selection and cherry-picking via treatment of straightforward thrombectomy patients outside the trials—but also discrepancies in expertise—as the most likely significant contributors to their negative findings.
“Expertise on how far you can go and which technique to choose within a certain anatomy or vessel course is much more crucial in MeVO thrombectomy compared to LVO thrombectomy,” Gralla says. “I would assume that results across different sites have been quite heterogenous. Detailed analysis will most likely show some sites with very good results and other sites with very poor results, which is probably due to expertise problems in distal-vessel recanalisation. And, from my point of view, all three trials tried to do things very pragmatically in terms of leaving the technique to the interventional neuroradiologists’ discretion and their inclusion criteria including a broad range of quite distal occlusion patterns. This might have contributed to the results, because a distal M3 occlusion in the superior truncus is much more difficult to treat with thrombectomy compared to the same type of occlusion in the inferior truncus, in my experience. The new generation of RCTs will learn from current results, have less pragmatic designs and be more selective when it comes to occlusion sites.”
In this context, another point Gralla raises pertains to the ideal role for thrombolytic drugs in MeVO stroke. He cites data illustrating that thrombolytics are more effective in smaller, more distal thrombi, while thrombectomy is likely to be especially advantageous in larger, proximal occlusions, potentially creating an anatomical “watershed” beyond which thrombolytics are preferrable.
“This is a landscape where we have to define what point we go to mechanically, and from what point we go with thrombolysis, because—for very small thrombi in more delicate vessels—lytics can achieve a high recanalisation rate while thrombectomy carries an increased risk of complications,” Gralla comments.
Further analyses of subgroups in DISTAL, ESCAPE-MeVO and DISCOUNT are ongoing, as the stroke community attempts to unravel the specific instances for which thrombectomy is appropriate. Multiple studies with stricter, more refined protocols compared to those trials are already being planned; Gralla’s own centre is set to be involved in one such investigation, and he believes that ever-increasing numbers of cases as well as thrombectomy-capable centres will aid ongoing efforts to conduct dedicated RCTs.
“Looking at the relatively poor clinical outcomes of non-recanalised MeVO strokes, this remains a problem that needs to be solved soon—but I’m pretty sure that, five years from now, we will have evidence for the use of mechanical thrombectomy and thrombolytics far beyond M1 and M2 occlusions,” he concludes.
