Perspectives from a neurologist and a cardiologist on LAA closure vs DOAC for stroke prevention

Welcome to EUROPCR26. My name is Lorenz Raber. I'm the director of the cardiac catheterization laboratory at Bern University Hospital and I'm very pleased to be joined by Professor David Seifke who is the director of the stroke unit at Bern University Hospital. David, welcome. Thank you very much. We just had a session together on the latest evidence on the topic of percutaneous LA closure to prevent strokes. We discussed two very, very recent trials, namely the CLOSURE-AF and the CHAMPION-AF trial. Now, while the overall outcomes I think are known to the audience, the first question that I would like to address to you as a neurologist is how you see the results in terms of stroke prevention. Yes, thank you, Lorenz. It's really a pleasure to be here and as a neurologist to have the opportunity to discuss those results and those trials. Of course, as a neurologist, I'm very much focused on stroke outcomes because these are the outcomes that matter for me and for my colleagues. I think it's an exciting time. We see that there are two large randomized controlled trials coming out giving a lot of evidence, actually. We see that overall the stroke rates in both trials were quite low, which I think is a good sign because stroke rates were low. Both trials reported ischemic stroke but also hemorrhagic stroke, sometimes merging those different stroke types together, which for a stroke neurologist is a bit complicated because these events are not 100% comparable. Hemorrhagic strokes, very poor outcome. Ischemic strokes, very heterogeneous subgroup, but I think overall we see low rate and I think it's reassuring. In one of the trials, the CLOSURE-AF trial, we saw that the overall rate of even combining ischemic and hemorrhagic stroke was comparable between LAA, CLOSURE, and oral anticoagulation therapy. Even if you split it up into ischemic stroke, hemorrhagic stroke, you see comparable results and specifically for ischemic stroke, I think that is really reassuring. We would love to see also a difference in hemorrhagic stroke, of course, but probably the time is here key, the follow-up time, so probably these curves will diverge later if the patient has longer follow-up. And this against actually a background of a very high risk population with a CHAT-SWASC score of 5.2 and a high bleeding risk and, as you said, closure. Also, the study is summarized as negative study. Actually, stroke prevention did work out. Exactly, that would be my take from the study. However, the primary endpoint, they lumped together bleeding and ischemic outcomes. What's your view on such a combined endpoint? Is that something which... I think we have to see it from two perspectives. One perspective is the regulatory aspect, so FDA, EMA, these regulatory bodies, they would like to see those outcomes, also all stroke outcomes. But in terms of intervention, we have a... Stroke is a very heterogeneous disease, so you have a lot of different causes of stroke and different types of stroke. From a very specific and very effective intervention like LIA closure, we would assume that it has a very specific effect in preventing cardiombolic strokes, which are the worst strokes. They would have a large clot in the cerebral circulation, having a lot of ischemic damage, leading to a significant amount of disability. This actually, if it prevents these types of strokes, is very beneficial. You summarized the findings of the CLOSURE trial, but in the CHAMPION, these were not exactly equal. What's your comment on the stroke prevention in the CHAMPION trial? That came a bit of a surprise to see that the overall rate of stroke, there was a 1% difference between the LIA closure group and the anticoagulation group, which was mainly driven by a 1% difference in the ischemic stroke rate from about 2.3%. And this comes a bit of a surprise. But again, I think we probably would love to see more details on these types of strokes. So, of course, if LIA closure prevents large vessel occlusion strokes, you're causing a lot of damage, but then you see some small strokes, which the patient actually, after one week, doesn't really remember that he had a stroke, while with an LVO stroke, he will remain in a nursery home. So it's a totally different perspective from the patient. This would be very important for patients, but also for caregivers, to see whether we can see more nuanced results within the stroke outcomes. At the moment, we see a 1% difference. This is worrisome for a neurologist. We don't want to see more strokes, but I think the details of the stroke also matter here. And of course, we should not forget what we prevent with this prevention, namely a very significant reduction in bleedings. There was a numerical difference in major bleeding, not significant, but a clearly significant reduction in bleeding that actually matters to the patient. Those that were leading to a medical action, we should not forget about this positive aspect. And this is something that was shown in the champion, but not in the closure, because in the closure, they just used major bleeding in their end point. But this is something very important for patients. I think many patients are worried about bleeding complications. So I think it's a very relevant outcome for patients. I, as a neurologist, I was asking myself from a technical point of view, how can you comment on the technical success of LAA closure in those trials? Is this comparable to your clinical practice, or what are your take on that? Yeah, that's a good question, because obviously it's a preventive measure. And if you send to us a patient that should undergo pericardial LA occlusion, you must be sure that we do a good job. And so safety is key. And I think there was a huge evolution in terms of safety over the last decade, an evolution that made out of an experimental treatment, really a very, very safe procedure. And I think champion makes proof of that. If we look at the periprocedural safety data, we note a 1.1% safety end point at seven days, which is mainly driven by 0.6% pericardial tamponade, and only in 1,500 patients, only one periprocedural stroke, no death at all, and very few tamponades. I think this really makes proof that this has become a very safe procedure as far as the Watchman implant is concerned. So in the catalyst, however, the situation was a bit different. They had like almost 6% periprocedural events, and no, in the closure AF. So in the champion, there was a 1.1% safety end point. And in the closure AF, actually, this was up to 6%. And it was mainly driven by periprocedural breathing occurring in the first seven days. And there, I think the key learning is that the patients included were probably a bit too old, too polymorbid, and frail. And the second conclusion is that probably it's not a good idea to keep patients who are at high bleeding risk under dual antiplatelet therapy. Rather, we should aim for a low-dose stroke treatment regimen or a single antiplatelet treatment regimen. So to conclude a bit, the safety is clearly there. There was a big evolution of the therapy in that regard. And based on the two trials, I think patients with high bleeding risk, they are ideal candidates. And patients who do not prefer to take DOAC are good candidates. What we did not discuss in this session is, of course, combined procedures with combining a PBI with LA occlusion, concomitant procedures. That was the Optum trial that looked at that and was also positive. But beyond that classical patient group that may qualify for an LA occlusion, what are new potential indications for LAC from a neurologist perspective? So which patient group might be very attractive for a percutaneous LA occlusion, in your perspective as a stroke neurologist? That's a very good question. And just as a reminder, as a neurologist, we see patients mainly in the secondary prevention scenario. So I see a lot of patients who have known atrial fibrillation, who are already taking anticoagulation, but who failed anticoagulation and who come with an ischemic stroke. We would call it a breakthrough stroke. Although the overall numbers are small, the patient that we see, it's very frequent. So it's about 50 percent of all atrial fibrillation strokes that I see or 10 percent of the overall stroke population. And in those patients, they usually come with large clots in the anterior circulation, so large vessel occlusion strokes. And we are desperately looking for better prevention strategies to prevent further strokes in those patients. We have some evidence from, for example, LAOS 3, a surgical trial where surgical LA occlusion was performed and usually patients, or many patients continued to be in anticoagulation therapy, that there might be a combined effect, combining anticoagulation therapy and left adipendous closure to prevent specifically those large clot cardiombolic strokes. And I think this is a way where I see, as a neurologist, a lot of potential for LAA closure in the future. There are trials ongoing. There's a LAOS 4 trial ongoing combining the combination of LAA closure and anticoagulation. But specifically for breakthrough stroke patients, we are running a trial called ELAPSE, where we're actually randomizing those patients who had just had a stroke on anticoagulation therapy to receive LAA closure on top of standard of care therapy or just continue LAA anticoagulation therapy alone, hopefully to prove that this is a beneficial treatment for this patient group. And I think they will largely benefit from it. That's a very interesting perspective. And we, of course, are looking forward to the results. So I would like to sum up. This was about PERCUT-NSLA occlusion to prevent strokes. We have a lot of emerging data that show that the procedure, if done by experts, is indeed very safe and can be regarded as an alternative to oral anticoagulation. But key is patient selection. We do note that there might be a signal in terms of the small increase in ischemic stroke. However, there is a big benefit in terms of reduction of bleeding. Typical candidates are those who are at very high bleeding risk, patients who do not prefer to take oral anticoagulation. But it's probably not a therapy that just should be given unselectively to all patients. And as you said, from a neurology perspective, there's a very interesting patient subgroup with excessive ischemic risk, namely those who suffered from a stroke under oral anticoagulation. A lot to come, a lot to be discussed, and we will see how this intervention will find its way in the future. Thank you very much for being with us, David, and thank you for listening. Thank you, Norbert.