Boston Scientific Corporation (BSX) Earnings Call Transcript & Summary

Welcome, everyone, both here in the room and on the webcast today. We're excited to welcome our cardiology leadership team, but before we get to that, I'm going to go through some housekeeping items. First, we'll be providing forward-looking statements, so typical safe harbor and risk factors apply. Second, here are some of our regulatory and financial disclaimers. And with that, I'd like to hand it over to Joe Fitzgerald, Executive Vice President and President of Cardiology Group.

Well, that was quicker than I thought, but thank you, Lauren. Good morning, everybody. Thanks for joining us. We have the majority of our cardiology leadership team here with [ Lance ], who runs our coronary and structural components; Jim Cassidy runs our WATCHMAN franchise; and then the well-known Dr. Ian Meredith, who covers everything in cardiology. So again, thanks for joining. I want to just give a perspective about -- a little bit less than a year ago, we organized all of our businesses that you see on this slide into one cardiology group. Historically, we ran Rhythm Management, the stuff on the right-hand side of the slide, as a separate operating division and interventional structural with WATCHMAN separately on 2 campuses in the Twin Cities. Today, we bring all of these businesses together, and this is again about almost a year old. I will say this, why are we doing this? Because we look at cardiology, the largest $30 billion serve market that Boston Scientific addresses. The 7%, so call that high single-digit, are growth rates. We as a cardiology group, collectively, we have more things than we can invest in across all of these that would all drive our growth. But what you're going to hear today, I'll close with a slide at the end of it, on why we're confident that we can take share in the broad cardiology space and be at a compound average growth rate north of what you see on this slide, and I'll cover that in a moment. I will say this, the vast majority of infrastructure that we have in cardiology is in each of these verticals. So what this is not is a big combined admin-heavy group. So we have really committed to funding these verticals. Most of our investment is, for instance, in Lance's group with dedicated R&D, dedicated marketing, dedicated focus and the same way for that could be said on the U.S. selling strategy as well. Our view of the market growth rate is below, I won't cover that. But collectively, our view of the cardiology $30 billion market, it will grow 7%, and we have high confidence we can be north of that market growth and be a net share taker over the next few years. Let's talk about this group's performance to date. I think this is one, at least contemporary example, where we grew global cardiology 10% in the first half. You see the U.S. growth being there at the high-single digits, international in the low double-digit growth. The key drivers on the bottom are products that we have on the market somewhere around the world and/or are on a glide path towards U.S., Japan, other market approvals as we speak, but very solid growth. When you look at our 4 pillars of cardiology, Lance's group, Interventional and Structural growing high single digits. WATCHMAN, strong 20-plus percent growth year-to-date. EP, 10%, which is probably slightly above market with a vision that, that will be substantially above market as we bring our portfolio across the -- to many markets across the globe. And then CRM and Diagnostics, which is our core pacemaker, defibrillator and our diagnostics preventives business and our ICM growing high single digits. So pretty proud of what we've done year-to-date and believe that is above market growth. So let me just give you a sense, and I got to give Ian credit because he drove this type of a strategy in our interventional and structural business. But the way we approach this, we have 2 major customers, interventional cardiologists/structuralist and electrophysiologists. And we're trying to execute a strategy, a new here. Mike talked about this a lot with regards to our M&A strategy being tuck-in, high strategic fit. And what we're trying to do is to develop the most comprehensive portfolio across the continuum of care of the disease states within cardiology. So we think about that as what products will enable us to access patients as access vascular beds then we think about how do we better understand what is going on. Examples of that, and this is by no means a comprehensive list of all the products in [ BOC ]. But our PCIG business, coronary imaging, [indiscernible] gives us a great ability to determine what you actually do to treat and support that patient. Same way with our Preventice acquisition. Going upstream into the ambulatory EGM drives better diagnosis, earlier diagnosis of patients, which then can lead to pacemakers, defibrillators, ablations, WATCHMAN, et cetera. And the same way on our investment 10-plus years ago in cardiology EP mapping, right? We saw that as a cornerstone to then drive all of the treatments and the follow-up that we need with patients. If I take this one level deeper, let's just think about that, let's apply that sort of nomenclature and approach and strategy. Now let's look at just AFib management. So in the access, obviously, we're about 8 months past the acquisition of Baylis. That gives us a very strong way out ahead of everybody, market share position and leadership position and how we actually get to the left atrium. If you think about understanding, I already mentioned the mapping, the navigation, the modules that go into our RHYTHMIA Mapping System, and obviously, the ambulatory short, long-term Holters, CEM, MCT. Then look down and I can say that we are the most comprehensive sort of suite of products that actually can treat patients with AFib, all the way from our titanium pacemakers with AF diagnostics, WATCHMAN and then our sort of 3-pillar strategy in EP with a 4 sensing catheter, a world-class cryoballoon ablation platform and then our offense with our Farapulse suite of products. And then surrounding all of that with support, whether it be procedure planning, pre-procedure CT planning, patient management and then, obviously, our LATITUDE platform, which also includes LATITUDE Clarity for our ICM product, which is LUX. So there's an example of how we're doing this specifically in the world of AFib. So with that, I'm going to pass it to Lance, and he'll give you a brief overview of what's happening in an ICTx.

Thanks Joe. Good morning , everybody. And as Joe said, I run our coronary businesses. I also run our structural heart and interventional heart failure. So pick off of what Joe said as well, this idea of having a portfolio to treat across the clinical spectrum. We're very proud that we still maintain our #1 market share in the coronary space, and that's because we have the broadest and most complete portfolio. The way we think about things is, first, you have to see what you want to treat, then you need to actually prepare what you want to treat, then you actually treat the vessel. There is multiple sources of data that continue to support that this is the right clinical pathway, whether it's the ULTIMATE trial, FANG trial, SYNTAX II, which show that if you use physiology and imaging, you will get better clinical outcomes. So I'll touch a bit on the AVVIGO imaging platform, completely redesigned by the system, that's new hardware, software, back-end systems that's being launched around the world as we speak. This is going to allow us to have the latest AI technology software features. And every year, you will see a major software release to do things such as automatic lesion assessment or other calcium detection. Our common 2 wires, our physiology wire. It is designed specifically to be kind of like a workhorse wire where you don't have to do as many wire exchanges so the procedure can be faster, less cost. Then our OPTICROSS HD, that is the flagship IVUS, high def 60 megahertz catheter that we use. When you put all that together, our imaging portfolio in the last 3 to 4 years has doubled, and we expect that growth to double over the next 3 to 5 years as well. If you look at the prepared segment of the portfolio, this is all about treating calcium. And we believe to treat calcium, you have to have a full portfolio, it's not just 1 device. So we have the WOLVERINE cutting balloon, hugely successful that allows you to kind of crack and get a little bit more expansion in the vessel for your stent apposition. Rotablator, many of you familiar with, it's been a core stable in our technology to get that channel through calcium so that you can deliver your stent. We've also got a new Rotasystem called ROTAPRO, which basically, we optimized the procedure, get rid of the foot pedals, make it much easier for the cardiologists. And we have a new wire rota drive wire, which again is an idea, can you get the more distal vessels without doing wire exchanges to go faster with the procedure and less cost. In terms of treating our DES portfolio, still #1 worldwide, and that's based on the innovation. We're one of the few companies that continues to innovate in drug-eluting therapies. So the 2 main innovations are the 48-millimeter. It's the longest stent that's available in the U.S. Very excited to continue to maintain that leadership there as well as our MEGATRON. This is a purpose-built stent for large vessels as well as super complex anatomies such as the [ osteo ] space. And those 2 technologies alone are allowing us to maintain that leadership position as well as a price premium that we get on those 2 products because they are unique above conventional DES. I'm really excited to kind of tee up the next topic, which will be our AGENT drug coated balloon. And basically, this could be a $1 billion market opportunity. So the name of our product is AGENT. It is the paclitaxel design product. And we just completed enrollment in the U.S. of this trial, 600 patients, 40 sites enrolled way faster than we thought. I think it's further proving the excitement about this technology. Primarily, the trial was designed to look at in-stent restenosis treatment, which we believe is about 10% of the PCI. So 10% of the patients have had a PCI are going to come back at some point with in-stent restenosis. And this technology is ideally suited for that versus putting in another stent, which could create further problems down the road. So that trial is designed to prove it's better than just doing plain old balloon angioplasty. We also recently additional data from Japan, where they did a trial for small vessel analysis against an existing paclitaxel company, and we're very pleased that [indiscernible] very similar clinical results in the small vessel segment. What's really cool about this, though, is that we have a unique excipient that we use the bond the drug to the balloon, which allows us to use less drug and get the same clinical results. The other piece about AGENT to know is that it's built on the EMERGE balloon platform, which is the same balloon delivery system that we use for SYNERGY. We believe that AGENT is going to be a real game changer because it's going to be really deliverable just like SYNERGY as we can get to the hard-to-reach vessels, and we can deliver a unique clinical result with about half of the drug dose. If you look at the other segments, again, to add to our excitement here is, there's probably another 20% of PCIs that would benefit from a drug-coated balloon, small vessel disease in addition to the in-stent restenosis, bifurcations as well as the acute coronary syndrome patient, which is the younger patient have a onetime acute event, try not to put metal in to preserve options for down the road. When you put all this together, this could be a $1 billion opportunity for us, and we are really, really excited to push this innovation forward. I'm going to switch gears a bit and talk about our structural heart portfolio. Again, the momentum, if you talk to our physicians, continues to grow around ACURATE. And the data and market share in Europe, 10% across all of Europe, 20% penetration in the accounts that we are actively launched in. And this is without the large valve size, which I will touch on in just a minute. We've now launched in 50 countries. We're in Canada. We're also in India now. Really excited about that, Brazil as well. And the reason that we're gaining momentum is because the super-annular design and some of the other features being super easy to deploy are giving us really good clinical data. Hemodynamics, the industry does not talk enough about hemodynamics. Hemodynamics are having a very low gradient are going to position us very well for the future. We have a super low pacemaker rate, and our PBL is also very, very strong. Then if you go to the right side, we are happy to announce that we've completed our 13-patient EFS for the large valve size, allows us to treat up to 29 millimeter. And some of the feedback from [ Professor Goolie ] says, it's very easy to use, same type of performance that we're getting in our other valve sizes. So we're very well positioned to continue to gain share, and we look forward to performing with ACURATE neo2. I do want to touch on a couple of other things. As I mentioned earlier, the hemodynamic story, the deliverability of the valve, combine that with cerebral embolic protection, and we believe we have a great story and a new brand to start really talking about. We know the low-risk population is the fastest-growing segment of the TAVR population to treat, and we believe that we have a great value proposition. When you combine the hemodynamics of ACURATE plus the commercial alignment that you can do with ACURATE plus cerebral embolic protection, [ TheraSphere ] being a brand for lifetime patient management, treating patients younger, giving them more options for their future as patients are living longer. So commercial alignment is really, really important because 75% of all TAVR patients are going to have some sort of coronary artery disease at some point in their life. So if you don't allow for coronary access with these TAVR patients, you're going to create significant problems. With commercial alignment and the way that ACURATE is designed, we are able to get great coronary access for the lifetime of the patient. Another interesting statistic is that there's a 0% moderate or severe commercial misalignment, which means it's very easy to get commercial alignment with the deployment of ACURATE to the native anatomy in the patient and allow nature to basically continue to perform in the body as it would before you put in a prosthesis. I'm going to shift for a minute and just talk briefly about cerebral embolic protection. Really strong data. We missed the primary endpoint, but we did achieve some really excellent data and disabling strokes for that I'm going to introduce Professor Meredith to talk about. But it's really important to know that when you talk to a patient about TAVR, the thing they're most worried about is having a disabling stroke. They would rather not survive the procedure than to survive and have a disabling stroke. If you have this type of a stroke, it's going to add over 4 days length of stay, going to cost well over $130,000 in terms of the care of that patient. And the long-term tragedy with those patients is significant. So we're excited that we have some really strong data, and that's going to be my lead in to our Professor Ian Meredith to go a little more detail into the clinical results.

Thanks very much, Lance. Good morning, everybody. And I'm sure most of you are actually at the presentation to over my slides of details of the trial to announce, but I think you've all seen the study. The first thing to say about the PROTECTED TAVR trial is, it's actually the largest structural heart randomized trial ever undertaken, and we're very proud of that fact. And it was undertaken during COVID and the trial was a real-world trial. There were very few exclusions. In fact, the only exclusion for the patients coming into the trial was, if they couldn't have femoral access. So it's essentially translatable to real-world practice. And as you know, the patients were randomized 1 to 1 -- 3,000 patients randomized 1 to 1 TAVR with central cerebral embolic protection or TAVR as a standard procedure. Now in order to actually [ ascertain ] stroke as well as we possibly could, all patients underwent neurological assessment by trained neurological professional, either a board-certified urologist, nurse practitioner or other trained professional prior to the procedure and at 72 hours or discharge -- prior to discharge. So we had a good neurological ascertainment of stroke as we could possibly achieve. And the primary end point was that clinical stroke, that's 72 hours or discharge, whichever actually came first. And as actually Lance mentioned, the prime -- we did not meet the primary endpoint, but there was a 21% reduction in overall stroke, that is stroke or whether it be minor, major, hemorrhagic or otherwise. We had a 21% nonsignificant reduction in all stroke. An important component of that endpoint and I emphasize that because this is not a composite endpoint, an important component of that endpoint was a disabling stroke. And there, we actually saw in a secondary analysis, a significant reduction in disabling stroke. The worst type of stroke, dehumanizing, debilitating, disabling stroke. The thing that Lance actually pointed to before is as something that patients fear. And having done TAVR procedures myself for over 12 years, you were frequently faced during the informed consent process with patients when you explain the risk of stroke, disabling stroke and death, they would say, doc, I would sooner die than be left disabled and being spoon fed by somebody else. So that is meaningful to patients, that 60% reduction in disabling stroke. So I should add to that, that we undertook a significant number of secondary analysis. Now why do you actually do that? It's because everybody was looking for a potential smoking gun, a subgroup of patients in which the risk of stroke was higher, and therefore, the benefit of cerebral embolic protection might be greater. But what you'll see here -- and I apologize for the complexity of the data, but we're showing the complexity of the data because it's the image that's mostly important. This is a classic forest plot. The line down the middle is called the line of the Unity. Things to the left, favor cerebral embolic protection. Things to the right don't favor cerebral embolic protection. The dots are the point estimates of the effect within each of those subgroups, and you see there's 95% confidence intervals around all of those things. What it actually shows is uniformly whether you are old, whether you are young, where we had previous coronary disease or not, whether you had previous stroke or not, whether you are at low, intermediate or high risk of surgical risk or not. Whether you had moderate or severe calcium or low calcium burden, the benefit was due to formally and consistently across all groups in favor of cerebral embolic protection. Now obviously, the confidence intervals didn't prove statistical significance in each of these subgroups. But it's important to understand, particularly when you look at disabling stroke there in the right-hand panel that almost every one of those point estimates favored cerebral embolic protection. So what it tells us is, the effect was consistent and uniform across all patient subgroups. So we know that stroke, disabling stroke is unpredictable and wealth of data up to this point has shown an inability to predict a significant patient subgroup. And here, we've actually shown uniform consistent benefit of cerebral embolic protection across all patient subgroups. So to reiterate, we saw that the stroke overall, disabling stroke was significantly reduced. That is the one that patients most fear from and the effect of cerebral embolic protection was somewhat uniform across all patient subgroups, indicating that there was no significant patient population in where -- in which patients would benefit more than another. I think the most telling part about the discussion, if you were there yesterday for the late-breaking trial was the final question that Mark actually asked everybody. Mark [indiscernible] asked everybody. And despite all of the posturing about the statistics and the meaning and the interpretation and secondary endpoints when asked, would you use this that the treatment of a relative, and he did actually qualify that by saying, a relative in whom you liked or cared for. I think his exact words are relative you cared for, and the answer was uniformly yes. Accept, it was 7:1 and one said, no. So I think people will take this data for what it actually means in terms of disabling stroke. So if I could change gears a little bit and show one other piece of evidence that I think it's really important to draw to your attention. I do really hope that you actually saw the SCOPE I 3-year results yesterday. You may recall SCOPE I was an investigator-sponsored trial that was undertaken in Europe, very well conducted by Stephan Windecker and his colleagues, and we missed noninferiority by 0.1% in the primary endpoint, which was a 30-day endpoint with a huge composite of back-related safety and efficacy endpoints, and it was driven by a slight increase in paravalvular leak and indeed, acute kidney injury. And that was a trial undertaken with ACURATE neo, not ACURATE neo2 with the extended seal and improved PVL, but we suddenly missed the primary end point. But yesterday, they showed the 3-year outcomes. I'm just showing you the Kaplan-Meier curve there for all cause death, any stroke and hospitalization of valve-related dysfunction in 3 years. The lines are completely overlapping. Now whether you look to death, death and stroke or death, stroke and hospitalization, the lines were overlapping. Point number one, the 30-day outcome and the minor miss in noninferiority did not predict durability. And you heard about from Lance, the importance now with younger patients, the importance of long-term outcomes and durability. So I don't want to read too much into the Kaplan-Meier curves at 3 years. The data wasn't powered for anything other than to look at these composite endpoints over time. But you can see, there's no significant difference in the outcome in terms of death, any stroke or hospitalization. And this is the largest data set we have to date, and it is indeed with ACURATE neo, not ACURATE neo2, in terms of long-term follow-up in an objective independent study. What we did note, however, comparing the super annular technology, which actually had sustained improved hemodynamics at every time point across the course of the trial with a larger effective RFS area and lower pressure gradients right through the trial that when they started looking at a structural deterioration of the valve thrombosis and bioprosthetic valve dysfunction in the trends to improve outcomes related to the super annular technology. The surgeons always have tried to get the largest effective RFS area and best hemodynamics. The best hemodynamics provide you the best resistance against structural valve deterioration. So I think this is a very good data, and I think it bodes very well for our ACURATE neo2 platform with a extended field. But I thought it's important to draw to your attention these important data. And with that, I'll hand over to Jim Cassidy to outline the Boston story. Thank you very much.

Thanks, Ian. Great. So I'll start with the market, and it's amazing like the markets really come a long way in the past couple of years, and we really see that significant growth continuing. I think a lot of it's driven by patients, like patients with AF, higher stroke burden. It's amazing when the stats on that slide, 40% of those patients are completely unprotected, many of them struggle on blood thinners, and that's where the WATCHMAN therapy comes in. Just onetime procedure, longer-term scope protection for patients, alternative to blood thinners. And so we think about the growth really in 2 population tranches. One is the indicated patient population today, which we estimate is about 2 million, and it's highly underpenetrated as we look at it today. We'll continue to invest to grow the awareness of the therapy to strengthen referral pathways. And that's what you see driving a lot of the growth through that '24 time frame. And then the second population is around indication expansion. We have 2 studies that are underway today, the OPTION study and the CHAMPION study that could upwards of triple the indicated patient population for this therapy. The CHAMPION study, which is the larger of the 2 studies is comparing WATCHMAN to DOAC in an all-comers patient population. We expect to see the data from those 2 studies in the next 3 to 5 years. And if positive, we see that runway to a $5 billion overall market opportunity in LAAC on the back of that data. So there's a lot of positive tailwinds overall for the therapy. From a WATCHMAN strategy perspective, it's interesting because our strategy is really heavily formed and shaped by our early days in the market and that experience of launching a new therapy. So major focus on making sure those patient outcomes are right and everything you can do to ensure that. And the second big piece is that this is way more than a product. There's a lot that goes around this. So our strategy really reflects that. It's about the product. It's the procedure. It's everything that surrounds the product and procedure and ultimately starts with the patient. So you think about from a product standpoint, we launched WATCHMAN FLX now about 2 years ago, really exceeded our expectations across the board. You look at every single performance barometer for that product, it's really setting a new standard. It was great to see earlier this year at CRT and then again at HRS, the SURPASS data that showed in the real world how that product is performing. And probably what underappreciated is how much of that product is driving confidence from an implanter standpoint around the therapy overall. So it's been a really big growth driver for the therapy overall, the confidence folks have in implanting that product. Shifting gears to procedural side. I mean it's obviously very linked to the product. We spent a lot of time innovating across the procedural journey from early -- the pre-case planning side, we've got a proprietary software that helps clinicians plan cases called TruePlan, making it easier and more efficient in the procedure itself. We spent -- recently about 3 months ago, we launched the VersaCross connect product, which really marries the Baylis VersaCoss technology with the WATCHMAN delivery sheet. And in doing so, reduces the number of steps in the procedure and just streamline the procedure for commissions. And then lastly, on the post-implant side, which is where clinicians do spend a fair amount of time, 2 things. I think WATCHMAN FLX has really opened up same-day discharge as an option because of the safety and ease of the procedure. And then lastly, as many of you know, we got the -- expanded our indications for post implant drug regimes and now clinicians have a choice between DAPT and DOAC immediately post implant in that setting. So that's opened up things from a clinician and patient side. And then lastly, on the patient expansion piece, I hit already on the CHAMPION and the OPTION studies and kind of the potential impact of those studies. The other piece is that we're investing against the indicated patient population. Today, a significant investment in our digital assets and our campaigns, upwards of 200,000 patients in the past couple of years have come forward through those efforts. We've also spent a lot of time on our therapy awareness team, which is a team that calls on referring cardiologists and tripled the size of that organization. So combining those 2 elements, we think we can continue to drive penetration into this highly underpenetrated indicated patient population today. So if you look across the slide, a lot going on. There's a lot of strategic breadth here. What it's helped us do, it's helped us really partner with customers and the things that matter most of them, and it's on just the product. It's all the things that surround it, and it set us up well from a growth perspective overall. So then maybe lastly, speaking of innovations, we'll touch on a couple of innovations that are in the nearer term. The first is our steerable sheath. When you think about a steerable sheath, one of the biggest challenges within LAAC is getting the implant to land exactly where you want it within the anatomies because there are so many different types of anatomies. And so we're hopeful with the steerable sheath, just fine-tuning ability and the control that you'll get will make it a lot easier to get the product exactly where you want it with a variety of anatomies. So we expect to launch this product in the '23 timeframe. And we expect it to streamline procedures, particularly challenging ones and then also make sure that the position of the product and the anatomy is where you want it every time. And then we're super excited by the WATCHMAN FLX Pro, which our next-generation platform. It's built on the WATCHMAN FLX architecture. It's expanding the size matrix. It's adding visualization markers to the product to enhance alternative imaging modalities. And then lastly, it's a coded device as well. And so we know that within the space within LAAC, some of the challenges that are related to device-related thrombosis, the post-implant drug regime. And so this device is really designed to help create more consistent healing to reduce the likelihood of device-related thrombus and hopefully, enabling the future alternative post-implant drug regime. So that -- that product will be launching in the 2023 plus time frame. And we're excited by these 2 innovations that continue to further the growth of the therapy overall. So a lot of excitement in LAAC overall, and we're excited to continue to innovate in this space. And maybe I'll turn it over to Joe now.

Thanks Jim. [indiscernible] I said earlier that we have strong confidence in our ability to grow faster than the 7% sort of near to medium-term growth rate that we see in the broad cardiology market. When you look at our key growth drivers, as an example, we have 4 products that are late in their PMA cycle. You just heard from Lance that we fully enrolled AGENT that sets the clock as an example for a 12-month follow-up and then whatever we want to call it, 6- to 12-month approval cycle through FDA. So we have 4 of these products, which are all past that point of full enrollment and are barreling towards last patient followed and then approval. So as we look at our confidence in the '23 and '24 product launches that we've talked about 2023 and 2024, our confidence is very high. And then you see the fifth growth driver because we haven't disclosed a bunch on WATCHMAN FLX Pro. And as Jim talked about, we see that in the 2023 plus time frame with global launches commencing. So you've got 4 PMAs. You've got AGENT. You have force sensing catheter in EP, a cryoballoon system in EP, the Farapulse system and WATCHMAN FLX Pro in addition to Steerable Sheaths and many other supportive products. So that's what gives us confidence to be able to stand on stage and say, we think we can grow well north of market as you look at the near-to-medium term, just given the trajectory of approvals that are driven by successful clinical trials. So with that, I'll let Lauren tell you how we're going to do Q&A.

Great. Thanks so much, Joe and team. For the next 25 minutes, we'll take your questions, both here in the room and on the webcast. There's a little question box on webcast for those of you listening online. And we will be posting the slides at the conclusion of today's presentation before you guys ask.

Ali, why don't you just start with the several questions in the room and online. [Operator Instructions]

Travis Steed, Bank of America. Thanks for hosting this event this morning. On the SENTINEL data, obviously, reducing disabling stroke is the holy grail in neurology, as you said on stage, but the number needed to treat was pretty high. Does that matter? I'm curious if you think the data actually changes anything in practice? And do you need to do a study powered for disabling stroke?

So thank you, that's a very, very good question. If I can actually start with nominated to treat. Everybody know nominated to treat is one of the absolute difference between the treatment and control arms. So one over 0.8% is [ 125 ]. I think you need to put that in context of all stroke reduction therapies, whether they be secondary prevention of stroke or primary prevention of stroke. And if you look holistically, everything across medicine used to treat stroke, the number needed to treat ranges from 1 in 50 to 1 in 650. And so many of those therapeutic options take 3 to 5 years in order to reduce the rare risk of stroke. So that's the first point. So 1 in 125 may -- it depends on how you look at it from an economic perspective, but in terms of the nominated to treat against all other therapies, whether pharma or device, is well within the range of number needed to treat the therapeutic options whether primary or secondary protection. The second thing I'd say is, a practicing clinician for most of your life -- my life, patients are not interested in nominated to treat. When you do the informed consent process and you explain to the patients, you've got roughly a 1% risk -- or 3% risk of disabling stroke, and we can reduce that risk to a fraction of a percent or half that risk, that's what they're interested in. Because for the patient who has a stroke, even if it's a 1% to 1.5% risk, when they have a stroke, it's 100% risk for them. So patients don't necessarily see that. I think we've got to actually balance the economics with the disability, and as you know, Lance actually address that. With this, I'll go to the third part of your question and come back to the second part. The second -- third part of the question is, do we need to do a trial for disabling stroke? I think with these data, it's going to be very hard to actually randomize [ against ] control with disabling strike now that we've shown a 60% reduction. But importantly, we actually planned prospectively to undertake a second study, which is being undertaken in the U.K. and you heard alluded to yesterday called the PROTECT TAVI trial. That is a trial we've been doing in conjunction with the British Heart Foundation. The primary endpoint there is exactly the same, all stroke beat 72 hours or discharge. The time of stroke is slightly different, but it will be more lent towards disabling strokes. The importance there is, the trial will have 7,740 patients in it. We planned a prospective pooled metro analysis at the patient level, so we'll have data to look more carefully at these issues with nearly 11,000 patients. And the second -- the middle of your questions, I've forgotten.

Commercial impact. Lance, do you want to...

Yes, do you deal with the commercial impact.

Yes. I think it's an interesting question. And -- when you talk to the physicians, I think what Ian touched on the informed consent process, and I think some of the other pieces that Jim touched on direct-to-patient marketing, making patients aware of the therapy that there is an option to help them further reduce stroke. We're going to explore that as well, and we hope over time with additional data coming that this will change practice. Because again, the basic question is, you're physician, would you put this in your mother, maybe not your mother in law, but your mother, it's a pretty standard response that we would.

Joanne Wuensch from Citibank. Two questions. What did you think of the 3-year data for Amulet? Was there anything that you walked away with that that's interesting and to expect that? And then my second question is, Farapulse is sitting up there in Box number, I think, 1, 2, 3, 4. Didn't spend a lot of time on that, but I am getting more questions from investors on that. So if you could just give us a highlight on where you are in clinical development and commercial development?

So maybe Ian, and I will tag team the first question on the 3-year data. I mean, I think it was largely consistent with the 18-month results. I mean, I think our biggest takeaway is, again, it's a study against the legacy WATCHMAN device and watching the FLX really and all those dimensions as you look at the PINNACLE FLX, may be you look at the SURPASS data, the SEAL rates, the DRT rates, all of those are at a different level today than they were in that study. So to me, there's just no -- I don't know how impactful about that, that data set will be in the market.

Yes. No, I think -- sorry, yes, I think that's an incredibly important point. [indiscernible] 54,000 patients in CDR and also comparing WATCHMAN to WATCHMAN FLX, I think you need to take that into consideration as well. Look, there are a couple of take-home messages here. The beauty of the trial originally was that it was the largest study of left atrial appendage closure with [ ADVANTICS ], showing a reduction in stroke compared to what you would be for the CHADS-VASc score. So that's -- that was good. And what we saw at 3 years, there was a consistent reduction in ischemic strike. No difference in ischemic stroke between the 2 arms. No any difference in bleeding in the 2 arms and no difference in all course mortality. There was a lot of speculation around nonsignificant differences in cardiovascular death. Just remind you, the trial was not powered to look at cardiovascular death at the outset, and it is certainly not powered to look at cardiovascular death at 3 years and speculations on very small numbers within that seem to be less relevant. I think the topline message is the less actual [indiscernible], it's safe, and you can reduce your predictive risk of stroke, predictive risk of beading by those therapies. And I think the big point is, its WATCHMAN 2.5, not WATCHMAN FLX, and Jim nicely outlined all bandages with respect to [indiscernible] with WATCHMAN FLX.

So let me take the second part of your question, Joanne. So Farapulse, as we've previously disclosed, we have an IDE that is fully enrolled. So that's with the fair star generator and the fair wave catheter. That trial is fully enrolled. That has a 12-month endpoint. So as we've said previously, we're looking at [ 2024 ] approval for that system. The European launch, we are the only company today with a single shot electroporation CE Mark. That launch is going extremely well. I think you've seen some of that in our international data for our growth in our EP division. We are -- as you always have to do, we bought Farapulse a year ago, August '21. We have been working like night and day on the supply chain. That's surprise, surprise. That stuff that start-ups typically don't do super well. So we've made tremendous progress both on the catheter, the sheath and the generator of getting a robust supply into Europe. So in the second quarter, we ramped from, call it, a couple of dozen sites to substantially more than that here during the third quarter. We'll give more detail on that when we do our Q3 earnout. But launch is ramping in Europe, trial fully enclosed -- fully enrolled in the United States and no change to our previously discussed expectations for approval in the U.S.

Robert Marcus from JPMorgan. On WATCHMAN, you now have a competitor out there. I'd love to get your take on what you're seeing in terms of market expansion or a share split? And how much -- are you seeing one being used in a certain type of patients versus others?

Jim, do you want to...

Yes, sure. Yes, I mean I think you've seen the growth in the first half of the year. I mean the markets continue to be strong from a growth perspective north -- in the mid-30s from the first half of the year. I think, overall, having a second competitor in the market is helping that from that standpoint and just driving the awareness into new referral pathways. From the standpoint of share, we'll know more on the -- with the Q3 reporting in terms of where things end up from a share perspective, but we've been pleased overall with our first half overall growth. And from the standpoint of how folks are using that, the competitive product, I think I see different groupings. Like there was a group of folks looking at using it for DAPT specifically on the DAPT label. There are certain anatomies that are [ the Sabre one ] product versus the other the number of anatomies that fall into that category are really small. So folks that are using the products that tend to be less anatomy specific. They tend to be using it either for the DAPT -- historically for the DAPT label or just because of other historic kind of relationships.

I think what I would add to that is, I think we would attribute very little of the market growth due to the entrance of a second competitor in this space. Jim's group, we would pie-chart it to be our efforts on therapy awareness through this therapy awareness team drives the vast majority of that market growth historically. But I also think that ease of use, the safety, the time and the predictability of WATCHMAN FLX has helped that market growth as well. Why? Because in planning physicians the confidence that they can safely with very low adverse events, sub-1%, which is very different than just on anything we do in the heart. That confidence in being able to treat a patient, treat them safely and have whatever greater than 95% chance of getting off of meds after their 45-day echo and long-term anticoagulation, that confidence is a growing part of what's driving market growth. And we're 2 years into it, so that's not new news for us.

Vijay Kumar from Evercore. This is helpful. Maybe I had 2 questions, one on PROTECTED TAVR and one on your aging ISR trial. On the number needed to treat, right, is the math, the cost of system north of $1 million? And I think I saw Dr. Meredith share the $100,000 annual savings. Do the cost benefit -- does it make sense to you what percentage of cases or CP being used right now? What do you think that number could go? And then on agent ISR, what is the timeline? Can we see the readout at the end of next year? Or is this '24 timeline? And would Boston be the first company to have this differentiated label, what it means to the numbers?

We'll go reverse order. So we expect AGENT to be launched in the U.S. sometime in 2024. I think that was the gist of your second question. In terms of embolic protection, roughly 75,000 patients have been treated. It's roughly 20% of the eligible TAVR patients have been treated. So there's still plenty of room to grow. Interesting is that procedure time is about 4 minutes. So when you talk about the cost, the cost in terms of times just through the procedure 4 minutes to basically save somebody from a lifetime of disabling stroke. The cost is one thing. It's typically north of $130,000, but a 4-minute procedure that has a 94.4% effective rate in terms of safely getting through the procedure, we believe it's going to -- we're going to grow above the 20% market share that we have in TAVR.

Lance, to clarify [indiscernible].

Yes.

I think the other thing because your question, Vijay, was -- so if we fully enrolled the AGENT study 12 months from now, and that's a new disclosure. So in this quarter, we fully enrolled it. So last patient will be 12 months from that last patient enrollment. So we should see the data readout sometime in second half '23, probably late second half of '23. The other thing -- an interesting point, too, is -- one example is, we have more than one very large hospital system that wants to look at like the cost of using SENTINEL versus the cost they will bear, if they have a procedural stroke within that DRG. That is a very important point because that gets way beyond the incremental cost of SENTINEL and focuses on what cost does each hospital or hospital system bear if they have -- and I think now when you talk about patient consent, you have to talk with this contemporary largest TAVR study ever done. You have to inform patients, you've got a 3% risk of all stroke, minimum. And if you say some because there's a commercial device ready and available on the shelf, you'd say, it's probably not less than 3% because maybe some of the high-risk patients were treated commercially and not enrolled in the study. I think that's an important nuance about how the market will evolve and what the commercial impact will be.

Can I make just one more comment that number been to treat because it is something that was discussed a lot, but we never heard anybody really discussed number needed to harm. And so most therapies are considered on the number needed to treat and the number needed to harm. And here, we saw one major vascular complication in 1,500 patients. So the number needed to harm is 1 in 1,500. The number needed to treat to actually reduce a significant disabling stroke is 1 in 125. So when you review all of the different therapies, we need to also look at the flip side of the coin as to what number you actually need to actually create harm. And that has been 1 in 1,500 with DOAC.

Rick Wise, Stifel. If we could come back to [indiscernible] ablation, Joe, gosh, a lot of exciting products in the portfolio and opportunities. This seems to be one of the biggest and most exciting as we've discussed. And just when I think about my doctor conversations about the product, I hear seem to be words fast, quick, easy again and again. But I wanted to actually ask you now that we've got you in our clutches about some of the questions I've heard raised as well. And several recent conversations doctors are pointing to the early experience in Europe. And not just it's fast, quick, easy, but they're not really -- it's not really changing outcomes, it's sort of changing efficiency and sort of the fun and the speeds in the clinic, expressing concern about fluoro that the young doctors don't want to use that. How are you thinking about that? And an interesting comment from doctors just last week that they're not -- the indications for you is, if I remember correctly, he used to do at 32 pulses and doctors are so excited they're not doing the full amount, potentially impacting outcomes. So I appreciate I'm throwing some wild and crazy things that you -- but just wondered how are you thinking about the evolution of the technology from here? How are you going to address some of the concerns that I'm hearing? And just maybe talk about your education commercial strategy.

So a lot packed in there, Rick. So I mean I try to be really, really -- all right. So I think the other thing -- everything you said is the feedback, obviously, that we see in Europe. The one thing you didn't mention is safety, right? So the big promise of electroporation because it's nonthermal, electroporation can be thermal. Our version of electroporation, we work -- Farapulse worked 6 years, right, to get it to be a nonthermal. So I think that's a really important point because esophageal injury, phrenic nerve injury, the 2 things that physicians worry about the most when they treat -- electively treat an AFib patient is safety. Time will tell on the efficacy. We've got our IDE. We will be able to tell you in 12-ish month, right, what the outcomes are from an efficacy standpoint. We're not really doing anything different in PVI paroxysmal then, for instance, you might do with a single-shot cryoballoon, right? So that mechanism of action of isolating -- expertly isolating the veins. I don't know how confident anybody should be that we'll increase efficacy. We've seen some of that in the early publications from Vivik and others in Europe. But I think what we can honestly say is, there is a clear safety differentiator. There's a clear ease of use. We tend to remind everybody because there is a lot in the EP field of making it up as you go along. But our algorithm, which is essentially each vein gets 8 ablations that take less than 1.5 seconds each. If you follow that, you will get the results that we've published dating all the way back to 2019. So we're -- and we use our WATCHMAN model of how to support cases, how to be in the cases. There is no reason to veer today with fairway from our prescribed ablations per vein, it happens very quickly. And then I'll touch one last point on speed. So if you look at fire and ice as an example, that's the most contemporary data that how long does RF take, how long does cryo take? And both of those are in the 100-plus minutes and cryo is shorter than RF. The data that you just saw both in the manifest publications, the one at ERA and the one just recently at ESE, the other thing I think we can clearly say is, this procedure is faster as well as being trending towards significantly safer. But the speed and the replicability of a fair wave procedure and given our algorithm is clearly driving adoption because it's easy to learn and it's easy to replicate doctor to doctor to account. Last part of your question, we hear that, too. So today, in Europe, you either do -- Europe does fewer mapping, less snapping as a percentage of cases than the U.S. The U.S. does mapping in the 85-plus percent even if you include cryo. Today in Europe, it's either done under fluoro or they hodgepodge together something on their preferred mapping system to reduce the level of fluoro . Where we're going is that fair wave catheter and all of the other tools that are in development will be tied to our RHYTHMIA mapping system. And our goal there is to have 0 fluoro or low fluoro workflow. Now that won't happen today we get it approved. We'll get it approved, and then we'll have to submit some of the mapping modules, but it will be -- it's not years after approval, where we'll be able to offer a 0 or very low fluoro workflow tied to our RHYTHMIA mapping system. Could we auction off that question or we could monetize this.

Cecilia Furlong, Morgan Stanley. I wanted to just follow up again on SENTINEL. If you could speak to today in the market, what you're seeing in terms of economics as a barrier to adoption versus access versus kind of inertia. And then as you think about, I don't know if you have insight, but just trials that were unwilling to randomize in the study. What that percentage look like? And then lastly, just an update on SCOPE II, when we could see longer-term data out of that?

Well, do you want to do the commercial part of it, and I'll do SCOPE II.

It's a tough question to get the exact answers to, but there are economic rules that is a real issue. And it depends what institution you talk to, where they are really trying to clamp down. Other institutions are looking at more of the total cost. But to answer your question directly, it is a question that comes up, and we're going to have to continue to educate and make sure they're aware of the total cost of stroke as well as the total cost of what this procedure is in the scheme of all of TAVR. I think do you want to touch on the SCOPE piece thing as well?

Yes. So with respect to SCOPE II there, there is further follow-up of that data in SCOPE I finished 3 years. We would love 5-year [indiscernible] SCOPE I, having seen what we've seen in terms of trends in SCOPE I in 3 years, but there's not a further follow-up on SCOPE I and SCOPE II.

I think you were also asking about potentially selection bias. I believe that was the other part of your question with embolic protection. It's hard to say what percentage, but there were people that decided not to be in the trial from the very beginning because they did not want to have to go through randomizing patients they thought would benefit from the therapy. So that was a very real issue. Again, part of the reason to believe that maybe the stroke rates were underreported or that the incidence would have been higher if it was an all-comer sort of trial. The way the British U.K. trial is being run, it's basically, it's all patients. So there will not be a selection bias in that trial.

We did our absolute best when selecting slots sites -- [ 2 ] sites who agreed if there was equipoise and if they were able to randomize. If they felt that they didn't have equipoise, so they didn't believe that there was a role for randomization, we sort of avoid those sites. But within those sites that did randomize, we did still see some selection bias certain basis.

Yes. Just to kind of close that or connect the dots there. So the physicians that thought they could predict which patients might be at higher risk for disabling stroke, then that was where the selection bias came in. We believe this data is actually going to prove exactly that point. Disabling strokes are not predictable. We saw a benefit in all subsets of the patient process. Therefore, if that was their mindset that's going to further enable them to say that they should. They cannot predict. They're not God in the procedure. They cannot predict which patients are going to benefit from the therapy. Therefore, you should include it with all patients.

I think David [indiscernible] actually summed it up very nicely. He said, you either now, based on the data we actually have, chose to not use it or use it in every one because the data is fairly minimal and consistent with what we actually saw with respect to outcomes. There was no smoking down predicting one slot from one or another.

All right. Thank you so much. That concludes our event today. The replay will be available in about one hour on our Investor Relations site. And as I mentioned, our slides will also be posted in the very near term. Thank you so much for your time today.