and Vascular Group Investor Briefing here at ACC, both in person and on our webcast. For those of you on our webcast, please note the slides are available at our website, investorrelations.medtronic.com. Before we get started, I want to note that we could make some comments that could be considered forward-looking, and actual results might differ materially from those projected in any forward-looking statement. Additional information concerning factors that could cause actual results to differ is contained in our periodic reports and other filings that we make with the SEC, and we do not undertake to update any forward-looking statement. I encourage you to go back and read this slide. Quickly turning to the agenda. Today's event will last about an hour.
Mike Coyle, Executive Vice President and Group President of CVG, will make some introductory remarks before turning it over to Nina Goodheart, Vice President and General Manager of Structural Heart, as well as Dr. Jeffrey Popma, Director of Interventional Cardiology at Beth Israel Deaconess Medical Center, who will walk you through the results of the Evolut Low Risk trial. We'll turn it to Jorie Soskin, General Manager of Infection Control, who will discuss the TYRX WRAP-IT study results. We'll conclude prepared remarks with Mike Coyle, who will highlight the broader CVG pipeline. Following their presentations, the panel will be happy to take your questions.
All of the speakers I mentioned, in addition to Mike Weinstein, Senior Vice President of Strategy, Sean Salmon, Senior Vice President and President of our Coronary and Structural Heart business, Mike Marinaro, Senior Vice President and President of our CRHF business, and Dr. Peter Catanzetti, our Vice President and Chief Medical Officer of Structural Heart will be available to answer questions. With that, Mike, you want to get started?
Thanks, Mark, thanks to all of you for joining us. It really is a very exciting day for all of us. I always say it's a good day in any year when you actually get a publication in The New England Journal of Medicine, so to get two in one day is a very good day. Obviously, this is the culmination of a whole lot of work by a whole lot of people, investigators, people internally, to be able to complete both of these clinical studies and have them reported out meeting their primary endpoints. To me, both of these studies represent really the culmination of the clinical evidence for two areas of investment that have been very important to us over the past several years, infection control, really, which we've been embarking on for the last five to six years.
Then, of course, in the TAVR space, this is well over 12 years of activity to get us to this point on what we think is the biggest piece of clinical evidence that we've reported. On the TAVR side, obviously with low risk, very gratifying to hit the primary non-inferiority endpoint on the Bayesian design. I think also maybe even more importantly, they're showing very important superiority measures that we'll be able to review with you here today with Jeff Popma leading that discussion. Then obviously some very exciting data there relative to what we think will become increasingly important in low risk, the hemodynamic performance of the valve, things like patient prosthesis mismatch. We'll talk about that in this session this afternoon.
Then WRAP-IT, it too reached its primary endpoint, this is an area that has been a big focus for us just because of the magnitude of the impact that it has on patients to have infection. We have really a very unique technology with the TYRX product. Although it's a 510(k) and we could just continue to market it the way we did, we felt it was important to do PMA-like evidence generation for this product. Obviously, a 7,000-patient study is the largest clinical study ever done in the implantables area. Obviously very gratifying with its results. It will give us really a lot of data to work with for sub-analyses over the next one to two years that we think will be very helpful, including economic analysis.
Maybe even more importantly, it's really going to help us because of the uniqueness of the technology to basically through marketing and sales programs to drive primary market share in initial implants and in replacement. We're going to be targeting it as an important tool to grow in that segment. As Mark mentioned, we're going to go through the two trials first. I'm going to then come up, we sort of consider these data releases as the kickoff of our 2020 pipeline. I'm going to talk about some other 2020 pipeline technologies, some of our longer-term investments, we're going to open it up for your questions. With that, I think I'll ask Dr. Popma to join us, we'll start with the TAVR data.
Great. Thanks, Mike.
Thank you.
Great to see everybody. I'm going to go through this relatively quickly. We'll have a lot of time for deep dive during discussion, of course, all the real information is going to come during our question and answer session. I can guarantee that. You've seen this several times today so far. I'll just go through it quickly. I think everybody's familiar with this Bayesian design that we use for SURTAVI. Gives you a predicted posterior median. We found it to be 6.7% in surgery. We found it to be 5.3% for TAVR, which net a difference of -1.4% and with the confidence intervals met its non-superiority endpoint. The easy way to remember this is you just, it's one minus the 0.999, so the P value is really less than 001 if we were kind of doing some traditional statistics for this.
Not much question about the primary endpoint itself. We picked, as Mike Reardon has said, a hard endpoint, that came up in the guideline discussion just a little bit earlier today with Bob Bonow. Said to change guidelines, you got to have a hard endpoint. We picked 24-month all-cause mortality and disabling stroke as our endpoint. We thought that was important, and that's what we did, and this is how it worked out. I think we do have hard evidence that will support a guideline change for non-inferiority to SAVR. This is the real guts of the study. When we look at our all-cause mortality or disabling stroke rate at one year, a couple of things to note. We'd always felt that the rates for surgery were going to be very good.
All-cause mortality of major stroke rate of 2.5% at 30 days for surgery is pretty darn good. In fact, it's excellent. Of course, TAVR was lower than that. That was sustained up to one year. All-cause mortality numerically lower all the way through the one-year follow-up period. The disabling stroke rate, which is incredibly important to patients, statistically lower at one year. Because of P3, we just wanted to give a glimpse into what our all-cause heart failure hospitalizations, as it turns out, we had prospectively adjudicated it just like PARTNER 3 had adjudicated it. Although it wasn't in our listing as one of our primary endpoints, it was actually lower, numerically lower in those patients who received TAVR compared. Very highly statistically so. That benefit question came up today about when does that really occur? It's not the first 30-day hospitalizations.
It's actually hospitalizations that occur all the way through the follow-up period. That was pretty positive for hard endpoints of death, disabling stroke, and then hospitalizations. In the protocol, we had defined safety. We wanted to know was TAVR as safe as surgery in the first 30 days? The answer is it's safer. The endpoints that really drove that safety endpoint were disabling stroke, life-threatening bleeding, and acute kidney injury. It was 10.7% as a 30-day endpoint. In the SAVR group, it was 5.3%. In the TAVR group, it's about a 50% reduction, highly significant. As usual, Mike talked about this a little bit. Pacemaker rate was slightly higher in the TAVR group than the SAVR group, about a 10-point increment between the two. All-cause mortality for disabling stroke, atrial fibrillation, all lower with TAVR.
This was our go-to slide at the end because we wanted to be able to. I'm not wild about the cross-trial comparisons. Lots of discussions about what you can really do. You remember for both the trials, for P3 and for us, they compared to surgery. The only thing one can say about the benefit is the relative reduction between the two. It's not quite right to compare the point estimates between the two. We'll talk about that in just a second. This is a randomized trial, but we wanted to have some comparable data that put things together. As it turns out, if you got TAVR, the combined death, disabling stroke, heart failure, hospitalization was 5.6%, and it was substantially higher if you got SAVR, 10.2%. Really using the same endpoint, showing the same thing. That's what people have been saying all day.
These are all pretty comparable results between the two trials. These endpoints, although a little bit softer, are very consistent with what we saw in P3. This is the money shot. All you have been having to hear so far since 2011, and we presented the first TAVR data, was the fact that we're worried about long-term durability of your TAVR valves. Long-term durability. That's what we've been talking about. What we have shown consistency, and Mike emphasized all along the way, is that whatever time point you measure with the self-expanding technology designed to be the self-expanding technology, the grades are lower than surgery. This is out to two years. The NOTION trial now reports to six years. The rate of moderate patient-prosthesis mismatch in the NOTION trial was about 20% with surgery, 7% with TAVR.
We're holding up very well in the low-risk trial at two years and another low-risk trial, smaller numbers of patients, at six years. We're really getting very strong information about the hemodynamic stability of this valve. Patient-prosthesis mismatch is a big deal. On the right side is what happens at one year. Severe PPM, you're all aware of Howard Herrmann's TAVR article, but it's been showed by Stuart Head as well on the surgical side. Severe PPM is a bad thing, and it's four times higher with surgery than it is with TAVR at one year. That's not going to change. That number's going to be relatively consistent from what we've seen. There are some real hemodynamic benefits of this self-expanding technology, and we believe that this is really another step forward in answering the durability question that we've all been struggling with.
Patients feel better, they feel better in the first six months. It's important. You talk to a 75-year-old who's extremely active, they say, "Okay, how much is this going to lay me up if I have surgery versus how much does this lay me up if I have TAVR?" Read Gina Kolata's New York Times article for the best-case example of two brothers. One who got TAVR and one who got SAVR. It's great if you haven't read it. Big difference, this is the manifestation of that. The other piece I just want to reemphasize is this to Matt. Where's Matt? This is to Matt. Is that the relative reductions for all these trials are the same. Really, whichever one we pick, whether we pick the all-cause mortality or disabling stroke, we look at relative risk reductions.
Even though the frequencies are a little bit different, these yellow confidence intervals cross each other. There's really not any ability to take the point estimates from one versus the other and say that SAPIEN or Evolut would be better than one or the other. The same sort of thing as we look at all-cause mortality with disabling stroke at one year. All of these error bars cross one another as the point estimates are a little bit different. Given the small numbers of patients, the relative risk reduction using surgery as a control group is really not different between the two. What's this mean? Better hemodynamics. I think that that's going to be an important piece in this lower-risk population. It's because the valve is designed to be superannular.
We know that, we've talked about that for six years now. We also want to make sure that in younger patients, they had better hemodynamics. They do have better hemodynamics with the self-expanding technology, this forms the platform for long-term durability. I think we're in a really good place with that as well. Let me turn this back over to, is it going to be Mike or Nina? Nina, are you-
No, I can do this. I can do this from right here, actually. Thank you.
Okay, good.
As many of us talked about at CRT, we did an analyst briefing. We're looking at a market size of about $5 billion by fiscal year 2022, growing in the mid-teens in that same timeframe. We continue to look at our continued innovation. We're very pleased with our pipeline. We showed you that at CRT as well, we continue to look at indication expansion, particularly now in low risk, and moving into more and more geographies. We've been very pleased with the valve design, our supra-annular self-expanding valve. Dr. Popma just talked through the market-leading hemodynamics that we have seen across all of our trials, see now continued in our low-risk trial. Critically important, as Dr. Popma just said, in our younger, more active patients. We continue to see very strong procedural outcomes. We've got good PVL.
We saw that in the IDE trial, we're very pleased, again, with the safety of the recapturability and the repositioning of this valve. As we look across our pipeline, we showed you that as well at CRT, we continue to see continuous innovation across the platform. We'll continue to move that forward. Again, continuing to expand the indications. Very excited about the data that we saw, both from our trial and from the PARTNER 3 trial as we move patients into low risk. Of course, as you all know, in addition to TAVR, we look forward into the mitral space. We continue that leadership position. We still remain very confident and very pleased with our progress there, and we'll continue to update as we have more information to share. With that, Jorie, I think I turn to you.
Good afternoon. Different topic, but similar theme. When you take strong innovation and you put good evidence behind that, our patients get better outcomes, and we believe we can accelerate adoption of our therapy. That's candidly what WRAP-IT was all about. It was the largest prospective global randomized trial ever in this space. I'm grateful for the over 776 physicians, nearly 7,000 patients across 25 countries and 181 centers. A rigorously designed and really well-executed study. We saw strong equipoise across both arms, we also saw a really low loss to follow-up and crossover rates. Just phenomenal, robust evidence. A couple of things about the design and definitions of this study that are unique and worth reiterating. Dr. Tarakji talked about this was intentionally designed as an increased risk cohort.
These are patients undergoing any type of device revision, replacement, generator change, upgrade, or a de novo CRT-D. These excluded the highest risk patients. Patients that are well documented in the literature to already be at significant risk of infection, including those on dialysis, immunosuppressants, or prior device infection. That allowed us to clearly delineate where the infection was coming from, make sure it wasn't a recurrent infection, and provide even stronger evidence about the endpoint. We also had a really robust definition of major infection. This is different and unique from prior studies in this space. Major infections in the WRAP-IT study resulted in death, some type of meaningful subsequent intervention, extraction, re-intervention, change out multiple procedures, or a patient who was so sick that they couldn't undergo another procedure.
A really strict definition of a major infection that had meaningful consequence for the patient, both clinically and then cost for the system. As Dr. Tarakji shared this morning, achieved the primary endpoint, 40% reduction in major device infection at 12 months. What's notable is that the curve separates early and stays consistent through the duration. Not only at 12 months, but actually all the way through follow-up. Mean follow-up was about 20 months, and as you'll see on the curve on the right, that effect was sustained all the way through follow-up. Infection is not something that ends at 12 months. It's a risk that that patient carries through as you see the rates continue to increase over time. Again, early separation of the TYRX arm versus the control arm, that was sustained benefit through the study.
Infections are a catastrophic complication. Dr. Tarakji and the panel spoke about this this morning, certainly lead to increased morbidity, mortality, and cost. The literature would suggest 20% mortality at 12 months, 50% mortality in this population at three years, and costs anywhere in the range of $44,000-$83,000 on average, not to mention the outliers that certainly can be well in excess of those numbers. Significant impact for the patient, as well as consequences for the system. WRAP-IT provides the most comprehensive look at CIED infection. It also provides the most compelling evidence for use of TYRX in this patient population. Just to come back to the endpoint shared this morning, 40% reduction of major infection at 12 months, 61% reduction of pocket infection at 12 months. Safety endpoint was achieved. There was no trade-off clinically when using the envelopes.
We'll continue to investigate that and share more data later on that. That effect, as I just mentioned, was sustained not just through 12 months, but through the duration of the follow-up, and actually observed well out to the 36-month point. With the totality of this evidence, certainly we studied the TYRX technology. We learned a significant amount about CIED infection, but also compelling data for the Medtronic portfolio across our pacemaker and defibrillator portfolio that we'll continue to learn from as we move forward. Thank you. Hand it back to Mike.
Thanks, Jorie. Before I open it up, I know we typically do pipeline updates for you at the annual, or really the biannual analyst meeting. We haven't talked about the broader CVG portfolio since June a year ago. I thought I'd take a little bit of time just to talk about the upcoming FY 2020. As I said, we kind of think of this meeting as sort of the unofficial start to the pipeline there with these two data points, or these two sort of extended indication trials now being completed. There's more to it, obviously, that's coming, and I just want to talk about some of the bigger items that we would point you to. First, when CVG was formed back, I call the official date really FY 2011, when we organized the U.S. field under a CVG structure.
We also changed or decided really to double down on a strategy that basically shifted our internal R&D activity more toward disruptive technologies, moving away from sort of bells and whistles iteration to taking bigger bets in bigger markets. I think you can see some of the fruits of that effort here today with the presentations that were done. We're now in a position, I think, to leverage the data you see here and the design set you saw here in the TAVR side to not only grow the market, but we think to grow share. Obviously we can use the differentiation we now will be able to show quite definitively with the WRAP-IT data to differentiate our device offerings as well. I think they are only two of the things that we would point to as being important for FY 2020.
I thought I would focus in on that middle column and just talk about a few things that I think are probably the most exciting. First, beyond getting the expanded indications into low risk, which we think these data sets will obviously justify, we will also iterate on the CoreValve family again with the CoreValve Evolut PRO+. This will basically both reduce profile for the device. We'll be introducing a sheath with that product that will allow us to further improve the profile for delivery. Importantly, we will be taking the benefits of the Evolut PRO design throughout our entire device size range, including our largest device. We think that will really help position us well to take full advantage of the growth opportunity that we see from these data today. In addition, we'll be releasing the LINQ II product.
This is the first product that will be developed using our wafer-scale technology, where we actually put onto the hybrid not just the electronics, but also the battery. This will allow us to extend battery life on the product, take overall cost of goods down. We will be adding Bluetooth connectivity to this device and further extending the sensitivity and specificity of detection of arrhythmias and especially atrial fibrillation. This will also give us obviously two price points to play with within the insertable loop recorder market, which is important since we now can sell into the in-office market. That we think will be an important opportunity for us to get back into both market expansion and share capture mode. In addition, we'll be releasing a new family of ICDs, the Polaris family. This is a new platform for us.
It will include Bluetooth connectivity, also feature differentiation in terms of therapeutic features in atrial fibrillation and diagnostic features for the management of heart failure or patient management features for the management of heart failure. We'll also be releasing an active fixation quadripolar left heart lead with these technologies, which will be unique in the marketplace. As you saw from the WRAP-IT data, one of the big beneficiaries of the TYRX technology is the de novo implants of CRT-D. We believe we have multiple areas where we can both expand the price per procedure from those technologies, also take market share both in initials and in replacements. Of course, that extends to the traditional ICD line as well. We'll also be releasing into Europe toward the end of the year, the EPIX technology, the DiamondTemp ablation catheter.
We have done very well in the ablation market, growing at or above market rates for multiple years now with our Cryo technology. That has really been restricted to the PAF market or the pulmonary vein isolation aspect of the market. This will give us our first opportunity to go after the larger segment of focal ablation, which obviously is a real opportunity for us to expand our participation in the space. We're very excited about this technology, very rapid delivery of energy. It's true temperature sensing as opposed to the imputed core sensing, and we're hearing very good things from the investigators who've been involved in that study. We've completed enrollment. We have a CE mark.
We're just ramping up manufacturing. In the second half of the year, we would expect to launch that product into Europe. It will be a U.S. product in FY 2021. Obviously, the one that we are most excited about here is the Micra AV. We've had great success with the Micra product. It has been restricted to about 16% of the market as a true single-chamber device. It senses impacients in the ventricle. Generally, it's being used in patients with atrial fibrillation. Once we have the Micra AV, we'll be able to sense mechanical contraction of the atrium from that device, which is mechanically the same as what we have now, pace in the ventricle.
This will take us to being able to do what is essentially VDD pacing and open up about 55%-60% of the market to this technology at 3X price point that we currently play in. We are now sitting in the single-chamber pacemaker market at well over 60% market share because of the penetration we have with Micra. We think we have a real opportunity to drive significant growth in that area. We are targeting that product to basically come in either late this fiscal year, FY 2020, or by HRS of next year. An exciting new addition. One product I don't have on up here that we are poised to also launch is the IN.PACT AV drug-coated balloon. Obviously, with the announcements on Friday, we're taking a step back to see what kind of timing we can expect with a paclitaxel product like that.
We do have data sets completed for that and can file. It's just a question of how we fit that into the broader discussion of addressing the concerns about paclitaxel. That gives you a picture of what I think are the most important releases for FY 2020. We have a number of programs beyond 2020 that we can talk about. Since I would like to get to the Q&A, I'm just going to talk about four things that we're probably the most excited about. Obviously, the Intrepid transcatheter mitral program, we believe we have the lead in the replacement segment with this technology, and we continue to enroll in our clinical trial.
Next year, we would expect not only to continue enrollment now focused into the randomized phase as we are really working our way through the rolling phase, also to focus heavily on movement toward the transseptal system. We believe this is ultimately going to be the bigger of the segments in transcatheter mitral, and obviously, with two to three times the number of procedures versus aortic, we think it's one of the biggest opportunities we have, obviously within CVG and then really within Medtronic. Also on the Symplicity Spyral, we continue to enroll in the two pivotal trials for the U.S., that is the on-med and the off-med trial. We have not really updated you on that, and I would just give you the following data points.
We would expect to complete enrollment during the first half of next year, because of the 6-month follow-up period, we actually expect we will be reporting out data on that from the pivotal trial by spring of next year. This is a very exciting area for us and one that we think could be a really important growth vector for Medtronic. The extravascular ICD is a very exciting product from our perspective. It basically does not use intravascular leads. The conductor is underneath the sternum, and the device is placed much like a subQ ICD is, it's using a standard 40-joule output. We can use it in the standard can in terms of its size and its footprint. More importantly, that technology will enable both post-shock pacing and anti-tachycardia pacing, which are limitations of the existing technology that's available in the market.
We will be initiating our pivotal trial in FY 2020 for that technology. Finally, in our atrial fibrillation business beyond the EPIX acquisition, we also have internally developed technology called pulsed field ablation. This has been granted breakthrough designation by FDA because this technology basically does not rely on heating or cooling to do the ablation. It actually disrupts the membrane of the myocyte, therefore, in a very fast ablation in literally milliseconds, it is able to basically disable the myocytes within its field, which means most of the complications, virtually all the complications associated with ablation come from heating and cooling the wrong thing. By not having that heating and cooling, we think we can significantly improve the safety of ablation technologies both for focal and PAF ablation.
Again, very exciting long-term investment opportunities for us, things that we will keep you posted on major milestones for. As you can see, a rich pipeline for 2020 and maybe even a richer pipeline as we look into 2021 and beyond. With that, I think I will open it up to questions, and I think Mark is going to navigate out there, and we'll direct it to who knows the most, which usually will not be me.
Great. It's David, just two questions for me, maybe start with Jorie and then maybe Nina or Dr. Popma on TAVR. Jorie, just thinking about the WRAP-IT study, obviously, the relative risk reduction was very strong. The absolute reduction was obviously smaller. Number needed to treat was maybe close to 200. Doesn't it kind of suggest that this technology be used in even a higher risk population than we actually saw in this trial? What are the commercial implications of that number to treat, and how are you feeling about guideline incorporation and timing?
Good question and an important question. The first thing is back to the consequence, right? Relatively low rate of infection, which is good news for patients, for clinicians, and for Medtronic. Certainly, the consequences of those events when they do happen are catastrophic, squarely focused on that. The important thing that the study showed as well is that there were no trade-offs in that conversation. There were no safety risks associated, as that was shown in the secondary endpoint. The third piece, as we think about other analyses, certainly a robust data set we'll continue to publish on some of those more specific topics throughout the year.
As Dr. Tarakji mentioned today, the evidence in his opinion and clinical judgment showed strongly that in that population, in that increased risk population, which we believe is about 50% of the market, showed a meaningful patient benefit, again.
Guideline timing. Do you think this data is good enough for guidelines? What kind of timing should we expect for that guideline incorporation, if it happens?
Sorry about that. The guidelines, ultimately, that is up to the clinicians and the societies. Certainly, with the PADIT study last year, now with the WRAP-IT study, there's rich evidence for them to look at, and we'll defer to them, but believe that that is something that they will be looking at quickly in light of these two large studies.
David, I would point out that because of the size of the data set, we're going to be following on with more granular data about who benefited most. If there are accounts that want to deal with it differently in terms of valuing where they think it fits in their practice, we'll be in a position to do that for them.
Just to follow up on TAVR real quick. If I think about the clinician commentary from today, if you look about the low-risk market, two things are coming to mind. The most positive is the hemodynamic performance of this valve. Maybe there's some things they're trying to digest are pacing and coronary access, so this continues to be a dynamic. Dr. Popma, you can just talk about how you think clinicians deal with those two dynamics, positive and negative in the low-risk population. Maybe Nina, in what way does FX, N+, or Horizon start to address some of these dynamics over the next couple of years? Thank you.
That's a great question. Look, I think that we're still going to digest the relative benefits of two different valves and how they all fit together over the next years as that moves forward. You're right, there are relative trade-offs that we have in the current data sets now, pacemaker versus hemodynamics. Those are the only two things I could think differentiate the two. We're gonna do better with pacemakers because we only had a small percentage of the population we had in the trial had PRO, and our experience has been that PRO's pacemaker rate is actually much better. There's another ongoing study right now, OPTIMIZE PRO, that will be specifically looking at trying to lower the pacemaker rate. I do think that that's gonna be a little bit dynamic and get a little bit better.
We said in The New England Journal article, I think that's actually true, we have to see what the long-term implications of lower gradients are gonna be. Certainly, this has been a consistent theme that we've seen. Any way we look at it with respect to structural valve deterioration, I think that we're on the right side of the equation for longer-term durability with that. When we looked at how often we have to go back in and do reintervention, it's very low. Less than 2% of the time do we do that. Full disclosure, the SYNTAX score is very low in the study, patients who have very extensive coronary disease will probably be AVR coverage patients in the future at low risk. We do our work in our new designs. We certainly have worked out the issues of coronary access.
The newer designs maybe Nina can speak to are gonna address some of that too. I think we're gonna continue to learn from the trade-off. We think it's a good trade-off to learn because the one thing that we need to bring down, we can by better technology, better technique. The one thing that's been consistent is the hemodynamics through the entire time. Do you want to talk about Horizon?
Sure. Maybe I'll just add on to that. As we've looked at trial results, as we continue to think about the criticality of those hemodynamics, especially as Dr. Popma said, in these younger patients, we were very pleased to see the results in the Evolut trial. As we've said, we'll continue to work on getting that pacemaker rate down. We saw variability in that trial. As Dr. Reardon said, we had single-digit pacemaker rates in that trial. We know that that's possible. We'll continue to work on that. From a portfolio perspective, as we've shared with all of you, we have FX coming. We work on the repositionability of that valve, so we're excited about that.
As we move towards Horizon, which we've shared with you as well, we believe that's gonna be a valve that's really going to be designed to address some of the issues that you bring.
Let me just jump in here. Jeff, let me just have you chime in on this because one of the things that struck me today was it looked like the incidence of Left Bundle Branch Block, new Left Bundle Branch Block in the two studies was relatively similar. It was 22% at 30 days in PARTNER 3. The number was basically, what?
24%, Shane, I think.
24% for our trial. The incidence of creating the reason to put in a pacemaker looks like it was about the same, the two TAVR arms of the two different studies. Why are people putting in pacemakers more frequently for CoreValve?
Yeah. Absolutely, right. Look, as I said, we're going to dissect this. This is the first time we've seen a publication. We're getting into the supplements. We're figuring all this out. You're exactly right that the left bundle branch. Now remember, it used to be 40%.
Yeah.
It used to be 40% for most of our valves, now we're at 22%, so we're making progress. As an investigator group, we try to use good guidelines for not putting pacemakers in. Again, it's one of those things that now we've gotten all the other things worked out. We're going to focus with laser ability to be able to try to move down that rate because Mike's exactly right. Between the two different valves, the Left Bundle Branch Block , new Left Bundle Branch Block was the same. The LBBB is where we worry about LV dyssynchrony-
Yeah
particularly in patients with lower ejection fraction. It was similar between the two. We've focused on the pacemaker. You're right, we're going to have to dig more into the conduction abnormalities.
Part of that is just there's obviously a historical legacy view that self-expanding valves create Left Bundle Branch Block and are more likely to need a pacemaker. Is there a reflex there, they're more likely to put in a pacemaker? I just used the CoreValve-
Yeah. No, I think you're right. We just changed it. Initially, I think CoreValve did have higher pacemaker rates. In SURTAVI, we had a higher pacemaker rate. When we moved down to PRO, there's a difference in the conformation of the 9 mm at the annulus. It's more conformable. Then I think there's something about the pericardial wrap that actually protects the left ventricular outflow tract to get lower pacemaker rates. We've also made a design iteration. In contrast to that, again, I don't want to make too much cross-trial comparisons, in contrast to that, when we went to SAPIEN XT to SAPIEN 3 with the skirt, there was more bulk in the LVOT. We felt that there was going to be more parity of the pacemaker rates between the two than there was.
We observed in this study slightly more with Medtronic, with the Evolut. I think that is the area that we're going to focus on. We're going to get the 17% rate down to something that's much lower, and we're going to be able to fix that.
Rick Wise.
Thanks. Rick Wise, Stifel. Two questions for Dr. Popma. First, Dr. Reardon said it, Dr. Leon said it. This is a class effect here. Help us think through the implications of this wonderful data on adoption. Is this growth accelerating given the clarity of the data? Do we expect market growth to accelerate? Just a second question, I'll just ask it now. Marty said at one sort of throwaway comment that it's going to be very tough for other valves now given this kind of data set. Is that the right way to think of it? That this sets an even higher bar, or is that just Marty being Marty?
No. I have to say, I love Marty being Marty because I always learn so much. It's always great. No, of course. There are several steps that have to happen. The first step is the relief of aortic stenosis with low complication rates, as one can do by death, by stroke, by rehospitalization. We have safely relieved the aortic stenosis. We can do it better than we can do it with surgery. That is a consistent effect that we have seen, I think, with both trials. To be able to say the class effect is, yeah, fixing aortic stenosis with transcatheter therapy with these two devices does seem to be beneficial. That's profoundly good for patients, at least to two years with us and one year with the PARTNER trial. Now, is that true for every TAVR valve? Well, no, of course not.
I think that these two companies have gone through tremendous iterations to get where they are right now. I think the other vendors, or the other valve manufacturers, are going to have to go through a similar iterative process until they can actually get to a point where they have the kind of comparable results that we have right now. These numbers. Surgery was great. We never expected these kind of surgery rates in terms of the one-year mortality and stroke rates. TAVR did better than that. We never really even expected the surgery rates to be that low. That's a pretty high bar for new valves coming in. It's not to say they can't, and the sponsors are coming in to try to do new trials, but there's going to have to be some evidence base to document that.
I think that there will be a lot of time over time to sort out the nuanced differences between the two valves in terms of how they perform for the long-term and younger patients. I don't think we really have the data to be able to make that statement today.
Does this data accelerate-
No.
I'm sorry. Is this an inflection-creating data in terms of growth and adoption?
No.
Realization.
The team here is much smarter about what's going to happen. From my perspective, we have to go through several iterations. Bob Bonow was at the deep dive session. He said they're gonna, as quickly as they can, get the guidelines to change. ACC has to change, and they have to meet, and they have to update the guidelines for a lot of the payers to be able to weigh in. We have to go to the NCD, and we have to get the NCD updated for this particular piece, and we have to get FDA approval. Probably there will be a little bit of splay in the appropriate younger patients between now and then. I think we may see some risk creep.
What I think may happen, too, is now there's going to be even better penetration for the intermediate risk group, which we've sometimes been struggling with. I expect volumes to go up immediately, but not because necessarily with the low-risk approval. The totality of the evidence is just driving this thing forward again. I think a lot more of the patients at intermediate risk where there's some ambiguity about what's going to happen are going to get pulled in to get treated with TAVR.
Vijay.
Thanks, guys. This is Vijay Kumar from Evercore. Mike, maybe just talking about the market, to ask on the market acceleration question slightly differently. You have what, 80,000, call it TAVR mechanical valves being done with the data that's being presented, right? Bicuspid was not involved. What percentage of that 80,000 TAVR or mechanical is this data applicable to? Is half of them now TAVR eligible?
Let me turn that over to Nina, since she's the expert on it.
I'm going to turn it to Peter. Our cardiac surgeon.
Yeah. 80% of the surgical valves are with patients with an STS score under 4. Some of those patients also have extensive coronary disease, or they have double valves, triple valves. Those patients will still be for surgery. The isolated standard AVR, the gold standard is now TAVR. You have to have a very good explanation why you would do still surgery in those patients. If you think about the market, if we look across Europe and the United States, it currently is about 180,000 patients that are candidates for TAVR. With the low risk, you could potentially go up to 270,000 in Europe and the United States. If everybody adopts what we have heard today, that's a huge increase. Of course, it will take some time before we get there.
It's potentially a major increase that you can get because most surgical patients are still low risk.
Peter made those questions about mechanical valves, who gets those?
Yeah. Mechanical valves. In Europe, the age is about between 60 and 65 of patients that get under 60, 65 get a mechanical heart valve. In U.S., it's about 50, 55 the age range where patients get mechanical heart valves. I think potentially, that's exactly the biological valve market may change that dichotomy.
Yeah. That's helpful. If I may, one quick one. Mike, I want to understand, I heard the numbers right. Micra, you said 60% share. Are you gaining now, once you get the label expansion, is it safe to extrapolate you're gaining 10, 15 points of share gains in pacemaker at 3x ASP?
Well, remember, I'm talking about the single chamber, right? Where we're competing, that share is in a relatively small 15%, 16% of the overall market. Now we're talking about 55% opportunity. We are going to obviously aggressively position the benefits of the technology, the benefits of the technology are essentially, even though device implantation for a pacemaker is a relatively safe procedure, virtually all of the complications are associated with either the pocket or the lead. Now to be able to do true dual chamber pacing with a device in the sense of sensing and/or what's called VDD pacing, we think we can take what we've learned in the single chamber with all of the same implanters, with all the same procedural training, and simply expand the market.
Bob Hopkins?
Thanks very much. Bob Hopkins from BofA. Just one first quick one to start. It's a little off topic. I'd love to hear your opinions on what's going on with paclitaxel. The way I'd frame the question is, the FDA is clearly pointing to a higher risk of death if you use paclitaxel. Why is anyone going to use paclitaxel until we have a definitive outcome from their study?
Well, certainly, they're raising a very reasonable question, right? Our data has been public on this topic relative to our U.S. submission for years. Basically, that showed in the early data collection in years two and three, we saw numerically higher absolute rates of mortality in the paclitaxel arm versus the control arm. It was extraordinarily low mortality in the control arm. That was the principal observation that we saw. Of course, over time, those have begun to converge to the point where there is no statistical difference, even though there's still a numerical difference in our data at five years on the mortality rates between the two arms. What is new here is obviously the data from Cook's Zilver product has now been recast over the last few weeks. That has actually now shown something similar, but with statistical significance, as I understand it.
What certainly has occurred, which we didn't realize until really Friday, was that additional data has been reviewed. We would assume it's from the Bard PMA series that has now been layered into that analysis. Those three randomized controlled studies for U.S. approval are what are raising this question in the FDA's mind. To your point, they basically have said they would suggest other technologies be looked at in this interim period while we sort out what the challenge is. I do expect it will, in fact, limit the adoption or utilization of paclitaxel products here in the near term. Now, in June, they're bringing together industry and experts to review data.
There are many other data sets beyond those three data sets that are available to be looked at, including our Japan series, which was a randomized controlled clinical study, 100 patients, two to one randomized. It actually shows the opposite at three years, where in fact the rates of death are higher in the PTA arm than in the paclitaxel arm. We also have data from our IN.PACT DEEP study that is five-year randomized controlled clinical data that basically is in the below the knee area that also shows a numerically higher rate of death in the PTA arm versus the paclitaxel arm.
There is also a lot of work that can be done on the existing PMA study, because it was never designed as a mortality study, and we have lost a follow-up out to five years that we can now double down on and go find those patients and recast the numbers with updated data. All of that activity can take place, but between here and there, I have no doubt that we're going to see a significant reduction in the utilization of paclitaxel products. Now, I mean, what are they going to use? Stents, balloons, atherectomy devices. We sell all those we're expecting to replace a lot of that volume with our own product.
Thank you for that. One other just quick follow-up on TYRX from a cost perspective. Please correct my math here, but it seems like you need to spend $200,000 to save $60,000, given the number of patients that you need to treat to get a benefit. I'm sure something's wrong with that math. Could you help me?
First of all, the cost data that we have available today is retrospective from claims data sets mostly. It's not a perfect science. It gives us a range and an estimate. The WRAP-IT data will be the first time we've been able to go look at prospective evidence to highlight what exactly is both the time course of infection and the treatment for those patients and directly associating the cost with that. We're committed to publishing that data. We believe we'll learn a significant amount from being able to look at that prospectively as we think about that. In the interim, we anticipate that in the fall or by the end of the calendar year.
In the interim, as we think about the value equation, certainly we come back to the clinical consequence for the patient and the system, the cost to treat those patients, but also the opportunity to think, as Mike alluded to, across the portfolio on how we work with our customers to provide opportunities to address that.
Yeah, I would also just hasten to point out that the three-year mortality for patients who develop a device-related infection is 50%. This is not just a cost issue. I mean, this is a very serious threat to the patient. I bet, Bob, if you were getting one of these devices and you were in that group, you'd be insistent on the $19,000 being spent. The other thing I would point out is, as Jorie just kind of hinted at, we're the only ones who have this product. We're going to be pricing it appropriately into the marketplace. We can help those who are trying to pay for it with our broader portfolio through the differentiation of our product, and we think that's just one more reason to use Medtronic products.
Thanks. Larry Biegelsen in Wells Fargo. One for Nina, one for Jorie. Nina, on the bicuspid, patients in low risk bicuspid patients on the slide, it said that you're planning to do some kind of trial or something. I can't remember what the slide said. What's the plan there, and what % of low-risk patients are bicuspid? Then Jorie, on WRAP-IT, I read the sub-analysis in The New England Journal of Medicine paper that looks like there was no benefit in pacemaker patients, no benefit in CRT-D initial implants. It looks like the greatest benefit's obviously in replacements. Is that true? Why aren't you just focusing on that group of patients, which seems to be a higher benefit? Thanks.
Do you want to go first?
Sure. We'll take the second one first. I key in on how you phrased that, which is "looks like." Actually, as we were working with the journal on that, hypothesis-generating at best. Those data are not significant, and you can't make that conclusion from the studies. In fact, the investigators talked about that, and it was very clear from the statistician that you can't draw definitively those conclusions. Certainly, we'll continue to talk about that patient population that is at increased risk. There are multiple variables. Even if you are a low power patient, there are many other comorbidities that could put you in that higher risk category. Certainly, some of those data may be suggestive. I think that's why the physicians designed the trial the way they did.
You look clearly at other benefits, or excuse me, at other factors besides just the procedure type that could create risk factors for those patients. Something that certainly we discussed.
Larry, if I'm remembering your whole question, in terms of bicuspid, the way we've been looking at the market, about 40% of patients are low risk. Of all treated patients, about 40% low risk. About, what is it, half?
Half.
About half of those are bicuspid.
you had this slide
We have a bicuspid study starting in low risk patients. We're running through that now.
Pat Nixon.
Thanks. I had one question for Mike, if I could, just because it's a subject that's crossed over a few times between TAVR and CRM around Micra. We hear from clinicians their desire or hope that there might be some sort of pacer opportunity for a smaller, shorter term, shorter battery life, cheaper option. I'd love to get your thoughts on that, and then I have one follow-up on the data.
Well, in a prior life, Nina used to crawl the halls of the CRM business, making all sorts of contacts. She's the one who's actually been working this, so I'll have her.
Yeah, no, we've been hearing that from physicians as well, this interest in having a short-term temporary pacemaker. As I've said often, and Mike and I have talked about, nobody knows more about pacing than Medtronic. Our businesses are working together to address that. A high interest level, I think both from physicians and from our businesses, and so we're looking at that now. I don't know, Mike, if you want.
I was just going to add, we were just having that conversation 30 minutes ago.
Okay. Timeline's TBD or something?
Yes. Timeline's TBD.
Okay. Yeah.
There may be a role for LINQ, too, in a different configuration as well.
You can kind of bring everything together.
Exactly.
There's obviously great progress in stroke and mortality for both studies, and you talked about pacers, durability is still out there, but patient-prosthesis mismatch and maybe leaflet thrombosis to a lesser degree, but two things that are sort of in the haven't figured these things out yet sort of category, and I'd love, Dr. Popma, for you to give us some perspective on what you expect over the next six, 12 months as we kind of expand this indication. Do those get fixed? What have we learned, and maybe what's next?
In terms of the patient-prosthesis mismatch, do you mean that how do we get further down with the self-expanding technology or?
Yeah, it seems like we've learned a lot, even on the surgical arm, on the impact of that, and that's gotten better in sort of both arms. I guess maybe what do you see as the solution to that, and then what, if anything, is the next step?
No, that's a great question. A couple different ways to look at it. There was a whole session yesterday with surgeons talking about how they were gonna get better gradients, and there's certain surgical designs, and I don't know if anybody can talk about the surgical design, but maybe Peter can. There's surgical valves that actually are gonna provide better gradients. There was a big play that we have to do maybe root enlargements in some patients. Then there was a nice discussion about the valves that are specifically designed to do fracking and fracturing. That was a whole animated discussion. We can't call it fracking anymore, but that whole idea of valve fracture.
I mean, if I were going to pick the one thing with the hemodynamic PVL , where the winner is in the self-expanding technology, the supra-annular self-expanding technology, I think that data has been so consistent from the very beginning. I think that component of it is actually going to be a real advantage. As we can accumulate the data out to 10 years, I think these gradients are always going to be lower on the TAVR side, the self-expanding TAVR side than on the surgery side.
Yeah.
Yeah.
You saw the series that Martin presented that actually the gradients were better with the surgical heart valves, while in our series it was reversed. The TAVR valve was much better than the surgical heart valve. That's quite remarkable, I think, of his presentation.
Yeah.
Despite the fact that the little surgery was putting.
Peter, because really the discussion post today is, what prevents you from putting in a TAVR, right? Everything has shifted right now. It went from, "Who gets a TAVR?" to "Who doesn't get a TAVR?
Yes.
The pushback that's out there other than anatomical exclusions, like do we have the answer on bicuspids and
Yeah
and so forth is, we go into this discussion of well, the 1-year data looks fantastic, but we don't know about 5 years, we don't know about 10 years. You heard that discussion at the podium today. Maybe just touch on that because isn't that where the discussion heads after today? Is that's the last area of pushback is the durability question.
Yeah. I think Van's making a great point is that the 1 component that we don't know about is we did an HALT sub-study. Both companies did. Both sponsors did. We have 200 patients and 200 patients in both the different groups for these two trials. They're 1-year primary endpoints, so we're not going to really look at the data appropriately until we get there. Just to editorialize about it, the bovine annular valves are not the same thing as a superannular porcine valve. Let's just see how the data falls out. I'm betting that the difference in design, the thinner, the longer, the superannular, it should have less reasons to have leaflet thrombosis than the other valve designs. Even if you look at the Makkar data all the way through, maybe the point estimates are a little bit lower.
We can't really do it till we definitively see it, but I think that there's reasons to think why that may be good. We know that the valve durability is better. We know from The New England Journal edits that we got to wait 10 years before we can say anything definitive about this stuff. I hope we can just schedule this on the calendar 10 years from now. We can all come back here and to talk about whether that's right or not. Thank you.
Maybe to add to this, the RESOLVE and SAVORY that was presented at CRT that was mainly done by SAPIEN heart valves, the incidence was 40% leaflet thrombosis. There were only a few CoreValve in the study that didn't show any thrombosis. There's speculation that it might be better.
We have to have something a year from now, right? We have to have something to come back for a year from now. We're all meet with the HALT sub-studies. I think that that's a very, very good piece because really right now, as everybody has indicated, it's all going to be finding the right patients who are going to have good durability, quality of life for the long term. Those are the critical questions are left.
Okay guys, I think we're coming up to the top of the hour, bottom of the hour, I should say. One more question and then we'll go to Kristen Stewart.
Hi, thanks. It's Kristen Stewart from Barclays. Mike, I was just wondering if you could comment on just how we should put into perspective all that we've kind of learned at this meeting and then recent weeks too with paclitaxel DCBs. Should we think about it as, okay, you're going to have pressure with DCBs, but hey, there's upside from probably better than expected results coming out of these low-risk trials and then the WRAP-IT study that can help to offset that over the near term. How do you think about kind of the puts and takes here with all the news over the last week or so?
Well, certainly both of these studies are at or maybe even slightly better than we had expected when we were setting our guidance at the beginning of the year. On the other hand, I'm concerned about the paclitaxel impact and because of the replacement aspect of it in terms of that low per procedure cost of using traditional balloons and atherectomy. We're still working on what does all this mean in terms of how many patients are really at elevated risk such that they would take the risk, even though FDA has said what they've said. We know there's going to be a higher morbidity associated with procedures now because that's why people have been using drug-coated balloons is to prevent those redo procedures. We're going to see the market expand unfortunately over that time because of this.
We're also obviously going to have to then get very granular about who are the winners in terms of the portfolio without the access to paclitaxel products right across the board, stents, balloons, the whole thing. As you can imagine, this all came out Friday, so we're kind of working it. I'm sure we'll have more to say on our next earnings call about how to think about it, especially in the context of our plan for next year.
Everybody, thank you very much.
Thank you.