Good evening, and welcome to the Boston Scientific American College of Cardiology conference call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing star then zero on your telephone keypad. Please note this event is being recorded. I would now like to turn the conference over to Lauren Tengler, Vice President, Investor Relations. Please go ahead.
Thanks, Drew. Thanks everyone for joining us. With me to discuss our CHAMPION-AF and HI-PEITHO trials are Dr. Ken Stein, our Chief Medical Officer, Dr. Michael Jaff, Chief Medical Officer, Vascular Therapies, and Dr. Brad Sutton, Chief Medical Officer, AF Solutions. During the Q&A session, Dr. Stein, Dr. Jaff, and Dr. Sutton will be joined by Dr. Marty Leon, Study Co-Chair, Mallah Family Professor of Cardiology, Chief Innovation Officer and Director, Cardiovascular Data Science Center, Columbia University Medical Center. We issued two press releases earlier today of the data presentation of each HI-PEITHO and CHAMPION-AF clinical trials. The releases can be found on the Investor Relations section of our website. This call contains forward-looking statements regarding, among other things, our financial performance, business plans, clinical trials and product performance and development.
These statements are based on our current beliefs using information available to us as today's date and are not intended to be guarantees of future events or performance. If our underlying assumptions turn out to be incorrect or certain risks or uncertainties materialize, actual results could vary materially from those projected by the forward-looking statements. Factors that may cause such differences are discussed in our periodic reports and other filings with the SEC, including Risk Factors section of our most recent annual report on Form 10-K. Boston Scientific disclaims any intention or obligation to update these forward-looking statements except as required by law. In addition, this call does not constitute an offer to sell or the solicitation of any offer to buy any securities or solicitation of any vote or approval in connection with the proposed transaction with Penumbra.
Boston Scientific has filed with SEC a registration statement on Form S-4, containing a proxy statement of Penumbra and a prospectus of Boston Scientific that contains important information about Penumbra, Boston Scientific, the proposed transaction and related matters. At this point, I'll turn it over to Ken. Thank you.
Thank you, Lauren. Yeah, welcome. Good evening. This is obviously a very exciting time for us. Presented two very high quality randomized trials, both of which have the potential to be practice transforming. Before we get into those, I want to begin just a high level overview of where we stand right now, with our cardiovascular group. The group as a whole delivers today therapies that treat millions of patients every year. If you look at what's in development, we're working on therapies that have the potential to address disease states that affect over a billion people globally. I also want to remind you, we recently did change our reporting lines. I hope it's not confusing to everyone.
Right now, our cardiovascular group as a whole, which is led by Joe Fitzgerald, includes our Interventional Cardiology and Vascular Therapies group, which we now term ICVT. That includes vascular therapies and interventional cardiology. Separately, our Interventional Oncology and Embolization group, and then Cardiac Rhythm Management Diagnostics and our Electrophysiology and WATCHMAN divisions, which now fall under our AF Solutions group led by Nick. Before we get to the two trials that you all want to hear us talk about today, I just want to reiterate the overall strength of our clinical trial portfolio. I do believe it's one of the factors that differentiates Boston Scientific from the competition. I was talking to folks earlier today. If someone told me 10 years ago we'd have two papers in the same issue of New England Journal of Medicine, I'd have said you're crazy.
That's not all that's going on. Just a quick look at what's to come in terms of more important clinical trials. We'll begin our FRACTURE trial. That's the IDE trial to get Seismic approved for coronary use. We will be presenting that at the EuroPCR meeting in a few weeks. AVANT GUARD, our randomized clinical trial of FARAPULSE as first-line therapy for patients with persistent atrial fibrillation, will be presented as a late-breaking clinical trial at the Heart Rhythm Society. Down the road, I think very important to make sure we all focus on the THRIVE trial to get Tivus through its IDE approval for treatment of hypertension. AGENT DCB STANCE, a very important indication expansion trial for the AGENT drug-coated balloon.
Further out our expected VITALYST high-risk PCI trial, which we still do hope to begin at some point this year. That's not what you all are here to talk about tonight. With no other ado, I'm gonna turn things over to Dr. Michael Jaff.
Thank you, Ken. What a great day for patients with PE. Incredibly exciting day. As of yesterday, patients who came into an emergency room or presented in a hospital with such symptoms of a pulmonary embolus were largely managed by watchful waiting on a monitored bed and anticoagulation. If things went well, they went well. If things went poorly, they dealt with it. Oftentimes, the way they dealt with it was a very complex series of events.
As of today, that's no longer the case. HI-PEITHO was a large prospective multicenter international randomized clinical trial with meaningful clinical endpoints and independent adjudication of all those endpoints. 544 patients with intermediate risk pulmonary embolus, 59 sites, U.S., and eight countries in Europe. Half were randomized to EkoSonic plus anticoagulation, that is ultrasound-assisted catheter-directed thrombolysis, and half randomized to anticoagulation alone. The primary outcome was the seven-day composite of meaningful clinical endpoints, death from a pulmonary embolus, recurrence of a pulmonary embolus, which in every study has shown a bad prognosis, or the risk for cardiovascular decompensation or collapse. All of those endpoints were independently adjudicated. This was the primary outcome, statistically p of 0.005 in favor of EkoSonic plus anticoagulation over anticoagulation alone. This is a dramatic difference.
One of the big knocks on thrombolytic therapy and EkoSonic in the past has been that, sure, it may work, but you do it at the expense of major bleeding and catastrophic intracranial hemorrhage. In the HI-PEITHO trial, there was no difference in major bleeding at seven days and 30 days, regardless of the definition, ISTH or GUSTO. In addition, there was not a single intracranial hemorrhage in this trial. We are incredibly proud of this. The feedback we've heard so far has been incredible. With that, I will turn it over to Brad to talk about CHAMPION-AF.
Thanks, Dr. Jaff. Good evening, everybody. It's a full house. It's a long day for everybody, I think. We're going to talk about CHAMPION-AF. I want to put on my sort of clinician hat a little bit and talk about, think back to the days when I treated a lot of atrial fibrillation, albeit in the Stone Age before pulsed field ablation. Nonetheless, this is an incredible undertaking. The disease state is well known to you all. More than 60 million patients have this disease globally. It comes with a five-fold increased risk of stroke. We know that the mainstay of therapy here has been long-term oral anticoagulation. That comes with a couple of problems.
Number one, something like 40% or more of patients don't tolerate the medication or take the medication as prescribed long term, which comes along with an increased risk of stroke. Of course, oral anticoagulants come with the risk of bleeding. The CHAMPION-AF clinical trial is the largest prospective randomized trial in this space. The second-largest randomized trial we've run in this space relative to novel oral anticoagulants. 141 sites globally and 300 operators. A really broad experience of operators enrolling in this trial. CHA2DS2-VASc two or greater in men, three or greater in women, and randomized to WATCHMAN FLX. They could be on either DAPT or NOAC plus minus aspirin therapy for three months. What we're going to talk today about, as you saw from Dr. Kar's excellent presentation, is the three-year data.
Here you can see that we met our pre-specified primary efficacy endpoint, the non-inferiority endpoint, which was a composite of cardiovascular death, stroke, systemic embolism. I would point out a couple of things. Number one, if you look at the curves, they diverge, converge, and diverge, and converge a number of times. I think this is a function of the overall low event rates. I would point out here that the absolute sort of difference on an annualized basis between these two therapies with regards to ischemic stroke was 0.33%, right? Significant for non-inferiority and incredibly low event rates in both arms, suggesting that both therapies are reasonable for patients looking to reduce the risk of stroke in the setting of non-valvular fibrillation.
The primary safety endpoint here was the composite of non-procedural bleeding, both major bleeds and clinically relevant non-major bleeds. Let's talk for a minute about what is a clinically relevant non-major bleed. These are not nuisance bleeds. This is not bruising. This is not an annoyance. These are significant bleeds that impact patients' lives. They require an escalation of medical care. They require an emergency room visit or a change in medication. These are meaningful to patients, and we showed superiority with the appendage closure group over the oral anticoagulation group. Now, procedural bleeding was not included in the primary safety endpoint, but we did look at it in a secondary analysis, and this is an important slide for you to sort of take in.
The benefit remains true when you include procedural bleeding, with a 34% relative risk reduction in bleeding over three years, relative to oral anticoagulation therapy. It's a success slide. A number of secondary endpoints, pre-specified secondary endpoints underscore the safety and net clinical benefit of WATCHMAN FLX. First on the left is the non-inferiority endpoint around major bleeds. This is both procedural and non-procedural bleeds, so no difference there. The net clinical benefit, I think, is an important story. If you're a patient or provider, you're weighing risks and benefits of two therapeutic strategies. What you see here is the composite of cardiovascular death, stroke, systemic embolism, and non-procedural bleeding, and statistical superiority in terms of the net clinical benefit for appendage closure over anticoagulation.
To put this into context, I think there's a couple of really important points to make. Again, the annualized rate of stroke and systemic embolism in the WATCHMAN arm was 1.1%. How does that compare to the pivotal DOAC trials? If you look at the ARISTOTLE trial, which studied apixaban and led to apixaban approval, it's the most prescribed DOAC in the world. Annualized risk of stroke of 1.3%. In fact, this rate in the WATCHMAN arm in CHAMPION is as low as any of the pivotal DOAC trials. I think that's an important thing to keep in mind. That's still with an incredibly high compliance rate in the drug arm here, right?
A difference, again, of 0.33% per year between the two treatment strategies with an almost 90% compliance rate in the medication arm here. We know that's not real-world. We're very proud of this data. Again, the bleeding benefit preserved both when you include procedural bleeding and with the pre-specified safety endpoint. Finally, I want to just talk about the market opportunity here. Today, there are 5 million patients indicated for the therapy. We believe the CHAMPION-AF data paves the way to quadruple that number by 2030 and beyond. Twenty million indicated patients around the world. The bulk of those are in the U.S. If you take the 5 million today, it's three point five in the U.S., one point five outside of the U.S. We will be pursuing a label expansion.
The goal here is to position this therapy in eligible patients as a first-line alternative to oral anticoagulation. Of course, we're seeking and working actively now with professional societies to get meaningful interim guidelines updates and ultimately expanded coverage both with regards to CMS and the commercial payers, which we believe supports our previously stated market growth of 20% over the LRP. We're not stopping there. This is a picture of our fourth generation device. We're really committed to innovation in this space. This device really is uniquely architectured to close any appendage, regardless of the complexity of the anatomy. I would point out that IDE trial kicks off later this year. We expect to commercialize that sometime in 2028.
Then maybe one or two other things that I'd love to highlight here, the SIMPLAAFY trial, which we hope to present back half of this year. Reminder that that is a three-arm randomized study comparing on-label DAPT versus single antiplatelet therapy or half-dose DOAC. Really excited to bring that data to you all. We do have three late breakers that I'd be remiss if I don't mention at HRS coming up. Actually the one around the ASAP-TOO trial, which if you've been involved in this space for a long time, you may remember. Excited to give you a little bit of data on ASAP-TOO in contraindicated patients. On the EP side, AVANT GUARD, as was mentioned by Ken, is our first-line persistent AF ablation story randomized versus antiarrhythmic medication. There's one more. Ken, help me remember.
The study of CHAMPION-AF. Thank you. The prior ablation segment of CHAMPION-AF versus no prior ablation will be presented as a late breaker. With that, I'll turn it back over to Lauren.
Thank you, Brad. You did want to make the point that you couldn't have said it better yourself than Dr. Kar. That's what you left this slide with.
That's right.
Yeah.
Said it better than I did.
All right. That was the mic drop.
I totally missed my mic drop too.
He's like, it threw me the remote. Yeah. Awesome. So I know everyone's gonna ask, the slides will be posted on our website at the conclusion of the event, so you'll be able to see that. We are gonna open it up to Q&A for the next 20 or 25 minutes. In order for us to take as many questions as possible, please limit yourself to one question. I'll let my esteemed panel come up and sit down, and just raise your hand and someone will give you a. Maybe we'll start with. Yeah, go ahead.
Shagun Singh, RBC. Thank you for taking the question. I was just wondering with respect to next steps, how should we think about guideline changes, label changes, and then, you know, what impact do you expect from the study in 2026 prior to these label changes in NCD?
Maybe I'll just on sort of the broad picture. You know, we think this data supports, you know, our previously provided guidance of the 20% market growth. Maybe I'll let Brad or Ken speak to the guidelines and NCD.
I mean, I'll just reiterate what Brad said. Again, we do firmly believe that this data should support a label expansion. We will be submitting to FDA for that. We are working with the societies now in terms of getting a focused update to consensus documents, which would come before any guideline update. You know, once we get through the FDA process, the next step would be to work with CMS in terms of getting expanded reimbursement through the CMS national coverage decision.
Here. You can. Maybe in the front row over here. Just wherever.
Thanks. Thanks. Matt Miksic, Barclays. Thanks for taking the question. Maybe just, you know, maybe help us understand how you think about the near term effects before we get to the point of guidelines, NCD, et cetera. What challenges, if there are challenges in the clinical referral community, do you think that this solves or helps kind of move along? Thanks.
Dr. Leon, do you mind answering that?
Sure. Glad to. Well, first, guidelines tend to lag behind clinical practice. I think people are gonna look at this data, hopefully, as we do, that this is a very strong endorsement for the expansion of left atrial appendage closure with the WATCHMAN FLX.
In a much broader population than we've previously been confined to. You know, the current guidelines are pretty restricted. Right now, even in contraindicated patients, it's only a Class 2A indication. In the Class 2B indication in patients that are at moderate or high bleeding risk, which is well behind what we currently are doing clinically. You know, it's my feeling that these data with a 0.33% annualized increase in either ischemic strokes or systemic embolization versus about a 2.6% reduction in bleeding, that's gonna be a balancing act that's gonna allow us to be able to have meaningful conversations with patients.
You know, given the non-adherence even to DOACs, at least in my mind, it's likely that a significant number of patients are gonna prefer this single treatment option to what is currently available. Kind of interesting just to digress, this wasn't brought up this morning, but in the NOAC group, there were about 200 patients that crossed over. Of the patients that crossed over, more than 50% were because either patients or referring doctors decided that they really wanted to have a left atrial appendage closure device, and they felt, you know, necessary to indicate that. That's even before there was any data. It gives you a sense as to what physicians and patients feel about lifelong NOAC therapy as an option, particularly in older patients.
I think that that's gonna resonate with the community of people who have atrial fibrillation.
Thank you. Hi, David Roman from Goldman Sachs. Thank you for hosting this. I've done a bunch of web scraping today using AI to gather all the social media feedback from different types of physicians. I was hoping I could just read it to you and get your feedback on it. It says, "EPs scientifically interested but clinically cautious. Interventionalists most bullish see near term adoption upside and general cardiologists pragmatic gatekeepers slower to change behavior." I guess I'd just love to get your perspective on does any of that surprise you? What is the strategy. More what's now the go-to-market strategy that you have the data in hand here in terms of driving adoption?
Ken, do you want to start and then?
Yeah. So maybe I'll start and then Marty. Well, first of all, you know, you didn't need to go to AI to get those descriptions just the varying personalities in the specialties. That's sort of something we've all been dealing with for 30 years. No, I know, David. I know where you're coming from. I just would say that that's a damn pretty darn good description of all of us. And I think that's right. You know, the implanted community, as the people I've been talking to here, irrespective of specialty, I think have been uniformly. I'd almost say giddy with these results.
I think these results were as good as anyone could have plausibly expected in the implanted community. You know, I think general cardiologists rightly are a little more conservative, but that's why trials like this are so important. Having the strength of a 3,000 patient randomized clinical trial that hit all of its endpoints, having it in the New England Journal of Medicine is important. I think the biggest thing that people are gonna learn from this, I expect, and Marty, I'm very interested in whether you agree or disagree with me. This trial, we felt was a very big risk when we started it because this trial enrolled a very low bleeding risk group of patients.
I think, you know, the real question was, you know, in a group of patients that turned out to have an average HAS-BLED score of 1.6, could you really show superiority in bleeding? I think the biggest lesson that people are gonna get here is that there is just a lot of clinically important bleeding, even in people who are considered to be good candidates for the NOAC drugs.
Yeah, I completely agree. I mean, I think that, I mean, there are obviously differences between how electrophysiologists and structuralists and interventionalists and general physicians, you know, view things.
I think in the beginning that to a certain extent, and perhaps even rightly so, that left atrial appendage closure was tainted with some early procedural complications, and people were much more conservative about applying it to broader groups of patients. I think that was not unreasonable, but that's changed. If anything, look at the safety data in this study with over 100 sites, a global trial, a 1% overall procedural significant complication rate. That is striking, and that should allay a lot of the concerns about broader application. Whenever you talk about changing indications, I think you always have to weigh some of the primary efficacy effects versus what the safety is. The general practitioners are always going to elevate or embellish, not in a negative way, but they're gonna focus on safety.
I think one of the messages that we should really convey is that over a broad population of proceduralists all over the world, there's a very, very low complication rate with this current device. That is the current state of practice. I think that's also gonna drive therapy. It also builds confidence within the operators in terms of being able to expand this beyond the current indications of patients who are higher risk, or being non-suitable for anticoagulants.
Thank you. Chris Pasquale, Nephron. Very encouraging trial overall. I was hoping you could just comment on the ischemic stroke rate. Hazard ratio was 1.61. The lower bound was right at 1, and there's a five-year endpoint that isolates ischemic stroke and systemic embolization. How should we think about the relative risk over time in these two arms? Does the device risk become ameliorated because of endothelialization of the device itself? Just anything we can take that we might be seeing in two years from what we saw today.
Yeah, again, maybe I'll start and then.
Sure.
Turn things over to Marty. First, most important point is, right, the reason that that endpoint is a 5-year endpoint is because it's not adequately powered at 3 years. I caution against really putting too much into it. I think second, from a patient-centric standpoint, what's more important than specific types of stroke is all stroke or all stroke and systemic embolism. Again, you know, we very convincingly meet non-inferiority for the combined endpoint of cardiovascular death, all-cause stroke, systemic embolism.
You know, even if you do believe that there is a small difference in the ischemic stroke rate, and let's see what the five-year data play out, the rates in both arms are incredibly low, and the difference on an annualized basis is very small relative to the potential benefit in terms of reduction of clinically meaningful bleeding. I think the real important message out of this then is, you know, patients ought to be able to make that decision. Yeah, two points that I'll make. First, we didn't show the Kaplan-Meier curves of the ischemic stroke rates. Just didn't have time. I think that the way they organized the late-breaking trials was a little bit funny this year. The contextual discussion, I think, really cut away from being able to show more data and having a meaningful discussion.
In any event, if you look at those Kaplan-Meier curves at the end of three years, the difference in ischemic strokes is 3.2% versus 2%. That begins to separate at six months and is pretty flat between 1 and 3 years. In fact, between 1 and 3 years, there are 27 versus 23 events, and with the difference in denominators, that's almost identical. There isn't very much change over time as you go forward. I think that I would keep that in mind, and I don't expect that these curves are gonna continue to diverge and then we'll lose the potential of achieving non-inferiority. That's one point. Second point is we're talking about all strokes, all ischemic strokes. When you break them down into disabling versus non-disabling, about 60% of these strokes are non-disabling.
Now, what is a non-disabling stroke? It's a modified Rankin score of two or more, which means that you have difficulty riding a bicycle or playing the piano. It's not a very significant stroke. It's a low bar of stroke. What I'm saying is that the real significant strokes is even that much less. When you weigh that against the difference in bleeding, you know, that's a discussion I'd really like to have with patients who have difficulty adhering to anticoagulant therapy, even NOAC.
Thank you.
Thank you. Josh Jennings from TD Cowen. You reiterated the TAM expansion opportunity. I was hoping to just review now that we know the CHAMPION data. We saw the CLOSURE-AF publication in the New England Journal of Medicine last weekend. The discussion referenced OCEAN-LAAC, ALINE, and CLOSURE-AF. I was hoping to just get a review of why you think the TAM expansion opportunity is still fully in play. I think you've talked about this in the past, but now with everything on the table, maybe it'd be great to just review the impact of CLOSURE-AF, OCEAN-LAAC and ALINE. Thanks.
Yeah, I'll take a stab at that. I think it very much is still in play. The way I see it is it really becomes a question of patient segmentation and directing the appropriate therapeutic strategy to the appropriate patient. OCEAN-LAAC and ALINE were sort of highly selected, low-risk patients who had undergone a successful ablation, as proven by the fact that they were atrial fibrillation-free for a year of close monitoring, right? That is a very selected group of patients with very low CHA2DS2-VASc risk. That is not the appendage closure patient, not in this trial, not in commercial experience, not anywhere in the world. I think there is room for both strategies depending on the risk profile of the patient. I think CLOSURE-AF is an interesting trial.
Contemporaneously it's worth kind of point by point conversation, but in fact it's a much smaller trial with a composite endpoint, less rigorous study design with old generations of devices. You know, they screened something like 10 patients for every patient enrolled. It took years and years to get that trial complete. Really failed its endpoint because of the bleeding complications, very procedurally. Bleeding complications that we don't see, as Dr. Leon mentioned, with the WATCHMAN FLX device. It's our belief, frankly, that if that had been run exclusively with WATCHMAN FLX, it very likely would've been a positive trial.
Yeah, I have to tell you, I was really surprised that CLOSURE-AF got published in The New England Journal of Medicine. There was a lot of buzz about it after its presentation at the AHA. When you think about it, this was meant to be a real-world, pragmatic, investigator-initiated study that took over six years to enroll a fraction of the initial patients that they really intended to enroll based upon the initial study design and with a screen failure rate of 92%. Only 8% of the patients who were actually screened and consented were actually enrolled in that trial. The procedural complications were, the major bleeding was 5%, five times what it was in CHAMPION AF. Any potential benefit of having to stop anticoagulation was completely negated by the totally inappropriate complication rate in the first month.
With all of these caveats about CLOSURE-AF, what was nice about CLOSURE-AF was that the stroke rates were about the same. In fact, we're going to do a meta-analysis looking at ischemic stroke, and we're going to include CLOSURE-AF, and we're going to include CHAMPION, we're going to include PRAGUE-17 and OPTION, and I think you'll get a much better feeling for what the actual results are. That's a funny trial, and I'm just struck that people have really latched on to it. A very different patient population enrolled in a very different way. 46% of the patients enrolled were enrolled at three centers.
It's a very different study, so it's a little bit hard to interpret and really put it in the context of this 3,000 patient clinical trial that was, you know, done, you know, in a much more rigorous fashion that'll have five-year follow-up with a third primary endpoint to come.
Joanne.
Thank you. Joanne Wuensch. I'm curious how you think physicians are going to turn the switch on in thinking about accelerating enrolling patients. We talked earlier about that they're going to maybe wait for guideline changes and that they're a cautious group to begin with. I'm trying to think about if I'm a doctor that usually does, I'm making this number up, 20 LAACs a month, do I think in 2027 that's going to 30? I mean, I'm trying to think about how that changes the vision of not 2026 but in 2027 plus that. Lauren, this then becomes a question for you. You reiterated the Watchman growth rate of 20% in new LRP, but that was before we knew the results of CHAMPION. What does it take for you to say it's higher than that?
You want me to start?
Why don't you go first?
All right. Yeah. As we've discussed, we've always assumed that data from CHAMPION will be positive, as it was necessary to continue to expand the patient population for which we'll treat to support that 20% growth rate. You know, this data was positive, and we see it as supporting that overall market growth of 20%. I'll hand it back to the CMOs to answer the hard stuff.
Well, again, I guess you can do the math on the 20% and then answer, you know, your average one who's doing 20. Thank you for doing the 20 a month, by the way. We appreciate it. 20 would be going to 20 times 1.2, right? I think maybe the deeper part behind the question is, you know, we again see this as helping sustain that 20% this year because I think as we said before, you know, it does reinforce the current indication. Nearly half of the patients in this trial had an ablation within the prior year. I think it also helps reinforce the concomitant indication and referrals for that.
I think again, Marty, you know, was very eloquent talking about the safety profile, which is really, you know, very gratifying to me, given just how many centers there were and how many operators were involved in this trial. I think that also helps reinforce current referral pathway. It will take, you know, better representation in guidelines consensus statements. It will take a redo of the NCD in the U.S. to unlock, right, the larger opportunity for growth and, you know, likewise outside of the United States, where again, physicians I think are a lot more conditioned to hear a little more closely to guidelines and where reimbursement challenges are greater than they are in the U.S. It'll take the time for those things to play through in the international markets.
Great. Next question. Go to Peter.
Yeah, thanks. Peter from Deutsche Bank.
Yeah, I can jump into that. You know, I don't recall that actually reached statistical significance. It was near.
It didn't. It was close.
You know, there are plausible physiologic reasons to think that Japanese patients and East Asian patients in general are more prone to bleeding risk on anticoagulants, including the NOACs, than is a western population. It makes sense from first principles to think that the Japanese patients would have the greatest benefit in terms of reduction in bleeding events and be able to avoid NOACs.
All right, next question. Larry.
Thanks for taking the question. All right. Maybe a two-parter. Of the label and the NCD, how confident are you that FDA and CMS isn't going to want the five-year data? You always expected CHAMPION-AF to help with international. Ken, you just mentioned it. Does CLOSURE-AF make that a little tougher given it's a German study? Thanks.
Yeah, I mean, we wouldn't be submitting this to FDA if we didn't believe that the data support getting the label update. Again, once we get the label update, it is our belief that the data would support reopening the NCD and broadening the indication. Our hope would be that whatever they do come out with in the NCD would cover the full label. Yeah, I mean, CLOSURE, you know, is it gonna have more of an impact in Germany? We're very glad that it's finally published. I think, you know, on the one hand, there's certainly more awareness about it now that it's been published, you know, than there was after it had initially just been presented at AHA.
You know, I wanna come back again to what Marty said. I mean, I'm not here to bury CLOSURE-AF. I think there's a lot to praise in CLOSURE-AF. You know, the two points, and I think it's on us and on the, you know, the implanters of WATCHMAN in the community to get this message across are right. Number one, exactly identical stroke rates in a very high-risk population, so that there are now four high-quality trials randomizing left atrial appendage closure against the NOACs, all showing non-inferiority for stroke, and that's PRAGUE-17, OPTION, CLOSURE-AF, and now CHAMPION. Second, that trial failed because they had procedural complication rates and early bleeding rates that are not characteristics of what we see today with contemporary devices.
All right, we have time for one more question.
Maybe can you review, at 85% adherence to NOAC, what is the real-world adherence to NOAC? I think in the end, the average cost is $500 out of pocket for a Medicare population. I think when you present Watchman, it's gonna be zero. When you consider the low adherence plus the cost benefit of Watchman, how is that gonna be presented by Boston now that this data is out there?
Yeah, I can take a crack at that. I mean, I think it's an incredibly high rate of medication adherence in this trial. I mean, kudos to the investigators and their interaction with their patients. The real-world data is not that, right? The real-world data is something more like 60% compliance. I think what you've got in the trial, in the control arm here is really a best-case scenario for clinical outcomes with DOACs. I forget the second part of your question, sorry.
The cost.
Oh, yeah, the cost-effectiveness analyses in this space have always really fallen in favor of a one-time procedure versus a lifelong anticoagulant. You know, I think you've got an evolving landscape with DOACs becoming generic, but also the introduction potentially of Factor XI inhibitors. I think it's a little bit of a nuanced answer moving forward, but to be sure, cost is one of the reasons patients have difficulty with long-term adherence to the DOACs.
All right. Well, thank you for joining us today. We appreciate your interest in Boston Scientific. If we were unable to get to your question or if you have any follow-ups, please don't hesitate to reach out to the IR team, and Ann and Drew will provide the details of the replay on the webcast. Thank you so much.