Thomas Munger, MD: Hello, and welcome back to the Mayo Clinic Medscape video series. I am Tom Munger, electrophysiologist and heart rhythm chair at Mayo Clinic Rochester. Today we will be discussing the pros and cons of Watchman and other left atrial appendage occlusion devices for prevention of stroke in patients with nonvalvular atrial fibrillation. I am joined by my colleague, Fred Kusumoto, professor of medicine and expert in this area. Welcome, Fred.
Fred Kusumoto, MD: Hi, Tom. It is wonderful to be here.
Munger: To start, I want you to answer this question: What is the rationale for left atrial appendage closure anyway? What is the big deal?
Kusumoto: Years ago, our colleagues Joe Blackshear and John Odell found that most clots in the heart originated from the left atrial appendage. This is a blind pouch that is in the left atrium, and because of this pouch, there is slow flow in that area. When patients have atrial fibrillation, there is irregular activation of the atrium and slower velocities in this area, and so sludge builds up, and this is where clots form.
Munger: I gather that these clots then could embolize to other parts of the body, so eliminating that virtual space would actually reduce the risk of stroke. Do all the clots come from the appendage or do some come from other areas?
Kusumoto: The left atrial appendage has all sorts of nooks and crannies, and because of that and the slow flow, the great majority of clots form in that area, but not all clots form there. In patients without mitral valve disease, anywhere from 80% to 90% originate in this area.
Occlusion or Anticoagulation?
Munger: Who should be considered a candidate for the Watchman procedure as an alternative to the anticoagulants we prescribe right now?
Kusumoto: We should be guideline-directed for this. The most recent 2019 AHA/ACC/HRS (American Heart Association/American College of Cardiology/Heart Rhythm Society) guidelines for patients with atrial fibrillation outline the use of this procedure for left atrial appendage occlusion. They gave it a IIb recommendation. The recommendations are divided into Class I, Class II, and Class III. Class I means you really ought to do it, Class III means you ought not to do it, and Class II is that huge area in between where one can consider it or not consider it based on clinical characteristics.
We further divide Class II into IIa and IIb; with IIa, you would be more inclined to do it and with IIb you would be less inclined. They gave a IIb recommendation for left atrial appendage occlusion in patients who are not candidates for long-term anticoagulation. It is important to note that in their discussion of this recommendation, they said that oral anticoagulation remains the preferred method for reducing the risk of stroke.
Munger: I know concerns have been raised from recent studies suggesting that compliance with oral anticoagulation is poor, and in fact, I have seen data suggesting that even with the novel agents, compliance may be no better than 50% or 60%, so that's another thing to consider when prescribing this procedure as an alternative to those drugs, since many patients do not take the drugs consistently. What about aspirin? I know a lot of our viewers have looked at aspirin as an alternative to the anticoagulants in high-risk patients who cannot take anticoagulants or who are concerned about falls and such. What are your thoughts about aspirin?
Kusumoto: Studies long ago looked at aspirin use. One study, the Stroke Prevention in Atrial Fibrillation (SPAF) trial, suggested that aspirin had a significant benefit. The problem is that SPAF is the only one of the aspirin studies that showed a benefit. For this reason, many people think this is an outlier with regard to the other studies, and so the most recent recommendations for atrial fibrillation and stroke risk reduction suggest that aspirin has no use, and there is no recommendation specifically for aspirin in the most recent guidelines.
Munger: So I gather that if you are going to prescribe nothing, or effectively nothing, then not giving aspirin would be the current recommendation. You just follow patients who are on no therapy. This makes appendage closure perhaps a little more attractive as an alternative.
Kusumoto: It is interesting to think about aspirin. First, there were a couple trials, particularly a study called AVERROES, which took patients who were thought not to be candidates for anticoagulation and randomly assigned them to aspirin or apixaban, one of the new oral anticoagulants. The study found no increased bleeding risk in those patients who received apixaban compared with aspirin, while there was a significant reduction in stroke risk and systemic embolism in those patients taking the apixaban. Aspirin was used, however, in the trials looking at left atrial appendage occlusion and still can be used after the anticoagulation period has ended.
Munger: Yes. I suppose we cannot completely ignore aspirin, since many of these patients have multiple reasons for stroke, and some of them have vascular disease that still would benefit from an antiplatelet approach for a period of time. How about the general approaches to appendage closure? I know that Watchman was approved in 2015 by the US Food and Drug Administration (FDA). Are there other methods for closing the appendage that are approved now or on the horizon that may come into use in the future?
Methods for Closing the Appendage
Kusumoto: This is an area that is exploding. In fact, multiple devices have been designed to close the left atrial appendage. They can be divided into two types. One is an epicardial approach, where you place a suture or some sort of barrette or method that clamps shut the outside of the left atrial appendage. The other is an endovascular approach, such as the Watchman, where you plug the left atrial appendage. So multiple technologies are trying to identify the best ways to close the appendage, either from the outside or the inside. Having said that, none of those other techniques are approved in the United States.
Munger: I suppose it is critical with any technique that you can verify that the appendage is closed, particularly with some of the older surgical series that involved a hand-tying closure of the appendage. They found that there was not much effect on stroke risk and, in some patients, the risk increased if they did not actually close the appendage completely. So any of these techniques do involve verification and surveillance to make sure the appendage really is closed.
Kusumoto: You are absolutely right, Tom. As you know, when you make the opening smaller, the stasis of flow can worsen and there is potentially more clot formation in those areas. As you point out, older surgical literature suggested that a simple ligation, in fact, was ineffective in terms of providing a permanent closure to the left atrial appendage in most patients. And even with our endovascular approaches, leaks between the device and the wall of the left atrial appendage can still occur, and so surveillance is required.
Munger: Talking about the effectiveness of these devices, I guess the best data we have are the two randomized clinical trials of warfarin versus Watchman: PREVAILand PROTECT AF. How effective is the device when you compare it with long-term warfarin therapy?
Kusumoto: The studies are fairly consistent—not only the studies that you mentioned, but subsequent registries when compared with historical controls. The Watchman appears to be as effective as warfarin in terms of reducing risk of stroke. The big issue is, by not being on anticoagulation, do you then reduce the risk of bleeding and thus reduce the risk of other side effects that can be associated with anticoagulation? As you know, some recent registry studies suggest that this is true, particularly in our high-risk patient groups. It will be interesting to look at this when the National Cardiovascular Data Registry (NCDR) provides its initial data. I am on the steering committee for the NCDR left atrial appendage occlusion group, and I can tell you that while the initial abstract has been presented and a significant number of patients have been studied, I cannot give you the specifics with regard to complications at this point, just because those data have not been released. [Editor's note: The NCDR data have since been published in the Journal of the American College of Cardiology.] Nonetheless, it seems that this is a device that is becoming more widespread in the United States and seems to be associated with reduced complications when in experienced hands.
Munger: Yes, by following the registry data here in the United States, I have been struck by how the complication rates with implantation, including stroke in particular, as well as perforation, have declined over the past 15 years since the early trials were done. I believe that one concern FDA had with the release of the device in the United States after the first randomized trial was the higher incidence of stroke with acute implant, but that has fallen tenfold since that first randomized trial was done, according to the data I have seen.
I look forward to hearing about the NCDR data when they comes out, because I think it will be critically important to understand where and when the devices are best used in our practices. If you look at the stroke rates with current use, again, they are quoted as 1 per 1000. I am still intrigued about the reduced incidence of overall mortality in the last randomized trial that was done compared with long-term warfarin. I believe that is something else we will want to look at, particularly as we get further out, because anticoagulants still have risks as you continue following these patients, whereas an implanted device does not, at least to any appreciable degree.
Kusumoto: We do have to consider the fact that left atrial appendage occlusion has been compared with warfarin but there have been no head-to-head comparisons with the new oral anticoagulants, which I think all would argue are better therapies in terms of reducing risk of stroke or alternatively reducing risk of complications. I do believe that as we get more experience with this, important long-term data will be critical, but it is also important for us to acknowledge that the trials and the studies we have, at least the randomized studies, have not compared the left atrial appendage occlusion device with our most recent armamentarium of oral anticoagulants.
Munger: That is an excellent point. We do not have any randomized trials in that space, and that leads to my next question: Where are the major current knowledge gaps in this space? What important questions still need to be answered?
Kusumoto: We have already mentioned the first question. Remember, we have not tried to evaluate or compare patients with left atrial appendage occlusion and patients who are on one of the new oral anticoagulants, what are called direct oral anticoagulants. Again, I think fairly strongly, and with very little argument, these are better drugs than warfarin anticoagulation just because they offer a more stable anticoagulation milieu and are associated with reduced risk of complications.
The second issue is, remember that we have a big experience in terms of the direct oral anticoagulants. These studies included anywhere from 15,000 to 20,000 patients. Our analyses, at least in the prospective randomized controlled trials for the left atrial appendage occlusion, are much smaller. Having said that, however, the NCDR has data on at least 40,000 implants for the left atrial appendage occlusion. So I believe that as we get more experience, particularly long-term experience, as we see ultimately how these patients do in terms of stroke risk reduction, stroke events, or systemic embolic events and other complications down the line and more long-term, this will provide a lot of information and guidance with where best this therapy should be placed.
Munger: Fred, this was a terrific discussion. Thank you for these very important insights today. I look forward to talking with you again when we have that NCDR data out and readily available for the community to review. Thanks to our audience for joining us on theheart.org | Medscape Cardiology.
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Cite this: Pros and Cons of LAA Occlusion Devices vs Anticoagulation - Medscape - May 28, 2020.