For those of
you on our webcast, please note the slides are available at our website investorrelations. Medtronics.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 statements. I encourage you to go back and read this slide.
Now 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 Goodhart, Vice President and General Manager of Structural Heart as well as Doctor. Jeffrey Patma, Director of Interventional Cardiology at Beth Israel Medical Center, who will walk you through the results of the EVOLUTE low risk trial. Then we'll turn it to Jory Soskin, General Manager of Infection Control, who will discuss the TYRX RAPID study results. We'll conclude prepared remarks with Mike Coyle, who will highlight the broader CBG pipeline.
And following their presentation, the panel will be happy to take your questions. All of the speakers I mentioned in addition to Mike Weinstein, SVP of Strategy Sean Salmon, SVP and President of our Coronary and Structural Heart Business Mike Marinaro, SVP and President of our CRHF Business and Doctor. Peter Capatine, our Vice President and Chief Medical Officer of Structural Heart will be available to answer questions. With that, Mike, you want
to get it started?
Thanks, Mark, and thanks to all of you for joining us. It really is a very exciting day for all of us. I would say it's a good day in any year when you actually get a publication in the New England Journal of Medicine, so you get 2 in one day, good 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. And to me, both of these studies represent really the culmination of the clinical evidence for 2 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 5 to 6 years.
And then, of course, in the TAVR space, this is well over a dozen years of activity to get us to this point on what we think is the biggest piece of clinical evidence that we've reported. So on the TAVR side, obviously, low risk, very gratifying to hit the primary non inferiority endpoint on the Bayesian design. But I think also maybe more importantly or so very important superiority measures that we'll be able to review with you here today with Jeff Popman leading that discussion. And 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. So we'll talk about that in this session this afternoon.
And then RAPID, it too reached its primary endpoint and 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 and we could just continue to market the way we did. We felt it was important to do TMA like evidence generation for this product and obviously several thousand patients study is the largest clinical study ever done in the implantables area and obviously very gratifying to hit its results. It will give us really a lot of of data to work with for 7 analyses over the next 1 to 2 years that we think will be very helpful, including economic analysis. But 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.
So we're going to be targeting it as an important tool to grow in that segment. So as Mark mentioned, we're going to go through the 2 trials. 1st, I'm going to then come up and 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 and then we're going to open it up for your questions. So with that, I think I'll ask Doctor.
Fatima to join us and we'll start with the TAVRIS data.
Great. Thanks, Mike. Thank you, Tim.
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, and I'll just go through it quickly. I think everybody is familiar with this basing design that we use for Sotavi, gives you a predicted posterior median. We thought it was 6 we found it to be 6.7% in surgery. We found it to be 5.3% for TAVR, which met a difference of -1.4% and with the confidence intervals met its non superior endpoint. The easy way to remember this is you just it's 1 minuteus the 0.999.
So the P value is really less than 1. We were kind of doing some traditional statistics for this. So not much question about the primary endpoint itself. We picked, as Mike Weir has said, a hard endpoint, and it came up in the guideline discussion just a little earlier today with Lon Bono, said change guidelines, you're going to have a hard endpoint. We think 24 month all cause mortality, disabling stroke is our endpoint.
We thought that was important, and that's what we did. And this is how it worked out. So 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 cost mortality or disabling stroke rate at 1 year, a couple of things to note about note.
We'd always felt that the rates for surgery were going to be very good. And all cause mortality had major stroke rate of 2.5% at 30 days for surgery is pretty darn good. In fact, it's excellent. And of course, TAVR was lower than that. That was a state up to 1 year.
The all cause mortality numerically lower all the way through the 1 year follow-up period. The disabling stroke rate, which is incredibly important to patients, statistically lower at 1 year. And then because of P3, we just wanted to give a glimpse into what our all cause heart failure hospitalizations. It turns out we had prospectively adjudicated it just like PARTNER 3 had adjudicated it. And although it wasn't in our listing as our as one of our primary endpoints, it was actually lower, numerically lower in those patients who received TAVR compares, so very highly statistically so.
And 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. So that was pretty positive for heart endpoints. So 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 1st 30 days? The answer is it's safer. And the endpoints that really drove that safety endpoint were DSAILUX drove life threatening bleeding and acute kidney injury. It was 10.7% as a 30 day endpoint. In the TAVR group, it was 5.3%.
In the TAVR group, it's about 50% reduction, highly significant. As usual, Mike talked about this a little bit. The pacemaker rate was slightly higher in the TAVR group than the TAVR group, about a 10 point increment between the 2. But 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. Remember for both the trials, for P3 and for us, the comparative surgery. The only thing one can say about the benefit is the relative reduction between the 2. It's not quite right to compare the point estimates between the 2, and we'll talk about that in just a second. This is a randomized trial, but we wanted to have some comparable data to put things together.
As it turns out, if you got TAVR, the combined depth to septic stroke, heart failure hospitalization was 5.6%, and it was substantially higher if you got JAVR10.2%. So really using the same hip, but it was showing the same thing. That's what people have been saying all day. These are all pretty comparable results between the two trials. And these endpoints, although a little bit softer, are very, very consistent with what we saw in P3.
This is the money shot, right? 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 belts, long term durability. That's what we've been talking about. And 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 graders are lower than surgery.
This is up to 2 years. The NOTION trial now is the course of 6 years. The rate of moderate patient prosthesis mismatch and the NOTION trial was about 20% with surgery, 7% with TAVR. So we're holding up very well in the low risk trial at 2 years and another low risk trial smaller numbers of patients at 6 to 7 years 6 years. And so we're really getting very, very strong information about the hematologic stability of this valve.
Patient prosthesis mismatch is a big deal. And on the right side is what happens at 1 year and severe PPM, you're all aware of Howie Herman's TAVR article, but it's been shown by Stuart Head as well on the surgical side. Severe is a bad thing, and it's 4x higher with surgery than it is with TAVR at 1 year, and that's not going to change. That number is going to be relatively consistent in what we've seen. So there are some real hemodynamic benefits of the 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 and they feel better in the 1st 6 months. It's important you talk to a 75 year old who is extremely active and 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 Coladas, New York Times article for the nice case example of 2 brothers, one who got TAVR, one who got ZAVR, it's great if you haven't read it, big difference. And this is the manifestation of that.
The other piece I just want to reemphasize, this is 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, disabling stroke, we look at relative risk reductions, even though the frequency is a little bit different, these yellow confidence intervals cross each other. So there's really not any ability to take the point estimates for 1 versus the other and say that this is that what is what that SAPIEN or Evolut would be better than 1 or the other. And the same sort of thing as we look at all cosmotelate was the stroke of 1 year. So all of these air balls across one another is the point estimates are a little bit different.
But given the small numbers of patients, the relative risk reduction using Surgis control group is really not different between the 2. So 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 build that and we talked about that for 6 years now. We also want to make sure that in younger hemodynamics, so they do have better hemodynamics with the self explanatory technology. And this forms the platform for long term durability. So I think we're in a really good place with that as well. So let me turn this back over to is it going to be Mike or Nina?
No, I can
do this.
I can do this from right here. So thank you. So as we talked about, many of us talked about at CRT, we did an analyst briefing. We're looking at a market size of about $5,000,000,000 by fiscal year 'twenty two, 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. And 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 superannular self expanding valve that's Patna just talked through the market leading hemodynamics that we have seen across all of our trials. We now continue in our low risk trial, critically important, as Doctor.
Potman just said, in our younger, more active patients. We continue to see very strong procedural outcomes. We've got good PBL. We saw that in the IDE trial, and we're very pleased again with the safety of the recapturability and the repositioning of this valve. And as we look across our pipeline, we showed you that as well as CRT, we continue to see continuous innovation across the platform.
We'll continue to move that forward. Again, continuing to expand indications, very excited about the data that we saw both from our trial and from the PARTNER's III trial as we move patients into low risk. And then 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.
And so with that, Juri, I think I'll turn it to you.
So 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. And that's candidly what rapid was all about is the largest prospective global randomized trial ever in this space. Grateful for the over 7 76 physicians, nearly 7,000 patients across 25 countries and 181 centers, Rigorously designed and really well executed study, we saw strong equipoise across both arms, And we also saw a really low loss to follow-up and crossover rate.
So just phenomenal robust evidence. Couple of things about the design and definitions of the study that are unique and worth reiterating. Doctor. Tarachi talked about this is intentionally designed as an generator change, upgrade or a de novo generator change, upgrade or a de novo CRTD. These excluded the highest risk patients.
So 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. And this is different and unique from prior studies in this space. Major infections in the RAPID study resulted in death, some type of meaningful subsequent intervention, extraction, re intervention, change out multiple procedures or a patient who is so sick that they couldn't undergo another procedure.
And so a really strict definition of a major infection that has meaningful consequence for the patient, both clinically and then cost for the system. And as Doctor. Taraji shared this morning, achieved the primary endpoint, 40% reduction in major device infection at 12 months. And 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. So 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. And so infection is not something that ends at 12 months. It's a risk that patient carries through as you see the rates continue to increase over time. And again, early separation of the TYRX arm versus the control arm that was sustained benefit through this study. Infections are a catastrophic complication and Doctor.
Teraci and the panel spoke about this this morning, but certainly lead to increased morbidity, mortality and cost. The literature would suggest 20% mortality at 12 months, 50% mortality in this population at 3 years and costs anywhere in the range of 44 $83,000 on average, not to mention the outliers that certainly can be well in excess of those numbers. So significant impact for the patient as well as consequences for the system. RAPID provides the most comprehensive look at CIED infection. It also provides the most compelling evidence for use of TYRX in this patient population.
And 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 envelope. And we'll continue to investigate that and share more data later on that. And then 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 after the 36 month point.
And so with the totality of this evidence, certainly we studied the TYRX technology, we learned a significant amount about CID 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. So thank you. And back to Mike. Thanks, Drew. So before I open it up, I know we typically do pipeline updates for you at the annual and or is it really the biannual Analyst Meeting.
So we haven't talked about the broader CBG portfolio since June a year ago. So I thought I'd take a little bit of time just to talk about the upcoming FY 'twenty. And as I said, we kind of think of this meeting as sort of the unofficial start to the pipeline there with these 2 data points, these 2 sort of extended indication trials now being completed. But 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 day 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 and D activity more toward disruptive technologies, moving away from sort of bells and whistles iteration to taking bigger bets in bigger markets. And 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 in the designs that you saw here in the TAVR side to not only grow the market, but we think to grow share. And then obviously we can use the differentiation we now will be able to show quite definitively with the rapid data to differentiate our device offerings as well. But I think they are only 2 of the things that we would point to as being important for FY 'twenty. And 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. 1st, beyond getting the expanded indications into low risk, which we think these data sets will obviously justify, We will also iterate on the CorVel family again with the CorVelu Pro Plus.
This will basically both reduce profile for the device. Be introducing a sheet with that product that will allow us to further improve the profile for delivery. And importantly, we will be taking the benefits of the Evolut Pro design throughout our entire device size range, including our largest device. So 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-two 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 insertable loop recorder market, which is important since we now can sell into the in office market. So 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 and will include Bluetooth connectivity, but 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. And as you saw from the RAPID data, one of the big beneficiaries of the TYRX technology is the de novo implants of CRTD. So we believe we have multiple areas where we can both expand the price per procedure from those technologies, but also take market share both in initials and in replacements and of course that extends to traditional ICD line as well. We'll also be releasing into Europe toward the end of the year the EPIX technology, the DiamondTip 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.
But 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 force sensing. And we're hearing very good things from the investigators who've been involved in that study.
We've completed enrollment. We had a CE mark. We're just ramping up manufacturing. And in the second half of the year. We would expect to launch that product into Europe and then it will be a U.
S. Product in FY 'twenty one. And then obviously the one that we're most excited about here is the Micra AV. This is a we've had great success with the Micra product, but it has been restricted to about 16% of the market as a true single chamber device. Senses in patients in the ventricle and so generally it's being used in patients with atrial fibrillation.
Now once we have the Micro AV, we'll be able to sense mechanical contraction of the atrium in the from that device which is mechanically the same as what we have now, but then pacing the ventricle. So this will take us to being able to do what is essentially VDD pacing and open up about 55% to 60% of the market to this technology at 3x price point that we currently play in. So we are now sitting in the single chamber pacemaker market at well over 60% market share because of the penetration we've had with Micra. And 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 in this fiscal year FY 'twenty or at by HRS of next year.
So an exciting new addition. The one product I don't have on up here that we are poised to also launch is the AV fistula 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. But 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.
So So 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. I'm just going to since I would like to get to Q and A, I'm just going to talk about 4 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, but then also to focus heavily on movement towards the transseptal system.
So we believe this is ultimately going to be the bigger of the segments in transcatheter mitral and obviously with 2 to 3 times the number of procedures versus aortic, we think it's one of the biggest opportunities we have, obviously within CDG and really within Medtronic. Also on the SIMPLICITI Spy where we continue to enroll in the 2 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 And because of the 6 month follow-up period, we actually expect that we will be reporting out data on that from the pivotal trial by spring of next year. So 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 subcu ICD is, but it's using a standard 40 Joule output.
We can use it in the standard can in terms of its size and its footprint. But more importantly, that technology will enable both post shock pacing and antitachycardia 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. And then finally, in our atrial fibrillation business beyond the Epix acquisition, we also have internally developed technology called pulsed field ablation. This is a breakthrough 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 and 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 or just all the complications associated with ablation come from heating and cooling the wrong thing. And so by not having that heating and cooling, we think we can significantly improve the safety of ablation technologies, both for focal and PAF ablation. So again, very exciting long term investment opportunities for us, things that we will keep you posted on major milestones for. But as you can see, a rich pipeline for 'twenty and it may even a richer pipeline as we look into 'twenty one and beyond.
So 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. So just as David Lewis Morgan saying, just two questions for me, maybe start with Jore and then maybe Nina or Doctor. Padma on TAVR. So Jore, just about the RAPID study, obviously, the relative risk reduction was very strong. The absolute reduction was obviously smaller.
The number needed to treat was maybe close to 200. So, does that kind of suggest that this technology we use to give any higher risk population than we actually saw in this trial? So what are the commercial implications of that number to treat? And how are you feeling about guideline incorporation and timing?
So good question and an important question. The first thing is back to the consequence, right? Well, 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. And so 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. Then the 3rd piece, as we think about other analyses, certainly robust data set will continue to publish on some of those more specific topics throughout the year. As Doctor. Tarachi mentioned today, the evidence in his opinion and clinical judgment showed strongly that in that population, right, in that increased risk population, which we believe is about 50% of the market, showed a meaningful patient benefit, again, preventing a catastrophic outcome.
Guideline timing, do you think this data is good enough for guidelines and what kind of timing should we expect for that guideline corporation if it happens?
Sorry about that. So the guidelines ultimately that is up to the clinicians and the societies. Certainly with the PADIT study last year now with the RAPID 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 2 large studies. And 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. So if there are accounts that want to deal with it differently in terms of value and where they think it fits in their practice, we'll be in a position to do that.
Just to follow-up on TAVR real quick. So if I think about the clinician commentary from today, if you look about the low risk market, the 2 things are coming to mind. The most positive is the hemodynamic performance of this valve. And maybe there's some things they're trying to digest are pacing and always your coronary access always continues to be a dynamic. So I wonder, Doctor.
Palmer, you can just talk about how you think clinicians deal with those two dynamics, positive and negative, in the low risk population? And then, Nynina, in what way does FX, NG or Horizon start to address some of these dynamics over the next couple of years?
So that's a great question. Look, and I just I think that we're still going to adjust the relative benefits of 2 different valves and how they all fit together over the next years as that moves forward. And you're right, there are relative trade offs that we have in the current data sets now, pacemaker versus hemodynamics. So it's the only two things I could think differentiate the 2. We're going to do better with pacemakers because we only had a small percentage of the population that we had in the trial had pro.
And our experience has been the PROS pacemaker rate is actually much better. There's another ongoing study right now, OPTIMIZEPRO, that will be specifically looking at trying to lower the pacemaker rate. So I do think that that's going to be a little bit dynamic and get a little bit better. We said in the Neumann Journal article, and I think that's actually true, we have to see what the long term implications of lower gradients are going to be. But certainly, this has been a consistent theme that we've seen in any way we look at with respect to structural valve deterioration, then I think that we're on the right side of the equation for longer term durability with that.
We do when we looked at how often we have to go back in and do re intervention, 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. So patients who have very extensive coronary disease will probably be AVR coverage patients in the future low risk. And we do our work on our new designs. We certainly have worked out the issues of access, but the newer designs maybe Nieni can speak to are going to address some of that too.
So I think we're going to 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. And the one thing that's been consistent is the hemodynamic through the entire time. Do you want to talk about trials?
Yes. And 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 Doctor. Potman said in these younger patients, we were very pleased to see the results in the EVOLUTE trial. And as we've said, we continue to work on getting that pace rate down.
We saw variability in that trial. As Doctor. Reardon said, we had single digit pace rate in that trial. And so we know that that's possible we will continue to work on that from a portfolio perspective as we have shared with all of you will we have FX coming. We work on the repositionability of that valve.
So we're excited about that. And then as we move towards Horizon, which we've shared with you as well, we believe that's going to 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 looks 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%, same thing.
24% for our trial. But so the incidence of creating the reason to put in a pacemaker looks like it was about the same, the 2 TAVR arms of the 2 different studies. So why are people putting in pacemakers more frequently for corona? That is
the right. So look, as I said, we're going to dissect this. We're both this is the first time we've seen the publication. We're getting into the supplements. We're figuring all this out.
And you're exactly right that the Buffalo Ranch now remember, it used to be 40%. So it used to be 40% for most of our valves, and now we're 22% when we're making progress. So as an investigator group, we try to use good guidelines for not putting pacemakers in. But again, it's one of those things that now we've gotten all the other things worked out. Now we're going to focus with laser ability be able to try to move down that rate because Mike's exactly right.
Between the 2 different valves, the left bundle branch block, new left bundle was the same. The LVV is where we worry about LV dissynergy, particularly in patients with lower ejection fractional similar between the 2. So that we focus on the pacemaker, but you're right, we're going to have to dig more into the conduction abnormalities. It's kind
of just there's obviously there's a historical legacy view that self sustaining valves create more bundle bench block and are more likely to be the pacemaker. So there's that is there a reflex there to more likely to put in a pacemaker Because I just used to put
it in Yes.
No, I mean, I think you're right, but we just changed. So initially, I think CorVel did have I mean, everybody we have higher pacemaker rates. In Certavia, we had higher pacemaker rates. But when we move down to pro, then there's a difference in the confirmation of the 9 mill of the annulus, it's more conformable. And then I think there's something about the pericardial wrap that actually protects the alveoli tract
to get lower
pacemaker rates. So we've also made a design iteration. And in contrast to that, again, I don't want to make too much cross trial comparisons, but in contrast that when we went to SAPIEN Xt to SAPIEN 3 with the skirt, there was more bulk in the LVL kit. So we felt that there was going to be more parity of the pacemaker rates between the 2 than there was. And we observed in this study slightly more with METRONIC with the EMBLU.
So I think that is the area that we're going to focus on. We're going to get the 17% break down to something that's much lower. And we're going to be able to fix that.
Thanks, Rick Wise. Stifel, two questions for Doctor. Popman. First, Doctor. Reardon said it, Doctor.
Leon said it, it's the class of bacteria. 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 the second question, I'll just ask it now.
Marty said at one sort of a throwy 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 that this is set to even higher or is that just Marty being Marty?
I love Marty being Marty because I always learn so much. It's always great. No, of course, 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. And that is a consistent effect that we have seen, I think, with both trials. And so to be able to say the class effect is, yes, fixing aeryxinosos with transcatheter therapy with these two devices does seem to be beneficial, that's profoundly good for patients, at least to 2 years with us and 1 year with the partner trial. Now is that true for every TAVR valve? Well, no, of course not.
And I think that these two companies have gone through tremendous iterations to get where they are right now. And 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 we have right now. These numbers, surgery was great. I mean, we never expected these kind of surgery rates in terms of the 1 year mortality and stroke rates. And TAVR did better than that.
And we never really even expected the surgery rates to be that low. So that is 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 AMBRA patients. I don't think we really have the data to be able to make that statement today.
And does this data accelerate?
I'm sorry, does this data accelerate? Is this an inflection creating data in terms of growth and adoption?
I mean, the team here is much smarter about making about what's going on. But from my perspective, we have to go through several iterations. Bob Bono was at the deep dive session. Said they're going as quickly as they can get the guidelines to change. But that has to change and they have to meet and they have to update the guidelines for a lot of payers to be able to weigh in.
We have to go to the NCD and we have to get the NCD updated this particular piece and we have to get FDA approval. So probably there'll 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. So I expect volumes to go up immediately, but not because necessarily it was the low risk approval.
There's a talent to be evidence that's just driving this thing forward again. And I think a lot more of the patients at intermediate risk where there's some ambiguity that was going to happen are going to get pulled in to get treated with TAVR.
Thanks, guys. This is P. J. Kumar from Evercore. So Mike, maybe just talking about the market to ask on that market acceleration question slightly differently.
You have about 80,000 call it SAVR mechanical valves being done with the data that's being presented, right? So bicuspid was not involved. What percentage of that 80,000 SAVR or mechanical is this data applicable to them, right? Is half of them now TAVR eligible?
Let me turn that over to Nina since she's the expert on it.
And I'm going to TAVR
So 80% of the surgical valves
are with patients with an SCS score under 4. Some of those patients also have extensive coronary disease or they have double valves, triple valves. So 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.
So if you think about the market, so if we look across York and United States, it currently is about 180,000 patients that are candidates for TAVR. And with a low risk, you could potentially go up to 270,000 in Europe and the United States. And so if everybody adopts what we have heard today, that's a huge increase. And of course, it will take some time before we get there, but it's potentially a major increase that you can get because most surgical patients are still low risk.
Peter, may those questions about mechanical valves, who gets those?
Yes. So mechanical valves, so in Europe, it's about the age is about between 6065 of patients that get under 6065 get a mechanical heart valve. In U. S, it's about fifty-fifty 5, the age range where patients get mechanical heart valves. So I think potentially, it's exactly the biological valve market may change now to TAVR.
That's helpful. And if I may, one quick one. Mike, I want to understand that I heard the numbers right. Mitra, 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 the ASP?
Remember, I'm talking about single chamber, right. So we're competing. That share is in a relatively small 15%, 16% of the overall market. Now we're talking about 55 percent opportunity. We are going to obviously aggressively position the benefits of the technology.
And the benefits of the technology are essentially even though device implantation for pacemaker is a safe procedure, virtually all of the complications are associated with either the pocket or the lead. And so now to be able to do true dual chamber pacing with the device in the sense of sensing and called BDD 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.
Thanks very much. Bob Hopkins from BofA. Just one first quick one to start. It's a little off topic, but I'd love to hear your opinions on what's going on with paclitaxel. And the way I frame the question is the FDA is clearly pointing to a higher risk of death if you use paclitaxel.
So 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? I mean, we have been our data has been public on this topic relative to our U. S. Submission for years. And basically that showed in the early data collection in years 23, we saw numerically higher absolute rates of mortality in the paclitaxelon versus the control arm.
But it was extraordinarily low mortality in the control arm. That was the principal observation that we saw. And 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 5 years on the mortality rates between the two arms. What is new here is obviously the data from the COX ZILVA product has now been recast over the last few weeks and that has actually now shown something similar but with statistical significance as I understand it. And 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 VARD PMA series that has now been layered into that analysis. And those three randomized controlled studies for U. S. Approval are what are raising this question in the FDA's mind. So 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.
And 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, 2 to 1, 100 patients, 2 to 1 randomized. And it actually shows the opposite at 3 years where, in fact, the rates of death are higher in the PTA arm than in the paclitax arm. We also have data in from our IMPACT D study that is 5 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 after 5 years that we can now double down on and go find those patients and recast the numbers with updated data. So 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 paclitax products. Now I think what are they going to use? Stents, balloons, atrectomy devices, we sell all of it. So we're expecting to replace a lot of that volume with our own product.
And then one other just a 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 mean, what's I'm sure something's wrong with that math, could you help me? So first of all, the cost data that we have available today is retrospective from claims data sets mostly, right. And it's not a perfect science. It gives us a range and an estimate. The RAPID 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.
So will certainly 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. And then in the interim, and so and 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, I think, as Mike alluded to, across the portfolio on how we work with our customers to provide opportunities to address that. Yes.
I would also just hasten to point out that the 3 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. And I bet, Bob, if you were getting one of these devices and you were in that group, you'd be insistent on the $10,000 the expense. And the other thing I would point out is with as Julie 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, Wells Fargo. One for Nina, one for Jory.
Nina, on the bicuspid patients in low risk bicuspid patients on the slide, it said that you were going to 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 percent of low risk patients are bicuspid? And then Jory, on rapid, I was I've read the sub analysis in the New England Journal paper that looks like there was no benefit in pacemaker patients, no benefit in CRTD TD initial implants. So it looks like the greatest benefits obviously in replacements.
Is that true and why don't you just focusing on that group of patients, which seems to be a higher benefit? Thanks.
You want to go first?
Sure. We'll take the second one first. So I key in on how you phrase that, which is looks like. And 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 and
it's that the
investigators talked about that and it was very clear from a statistician that you can't draw definitively those conclusions. Certainly, we'll continue to talk about that patient population that is at increased risk and there are multiple variables. Even if you are a low tower patient, there are many other comorbidities, right, that could put you in that higher risk category. And so, certainly some of those data may be suggestive. Think that's why the physicians designed the trial the way they did.
And 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. So something that certainly we discussed.
Larry, if I'm remembering your whole question, in terms of bicuspid. So the way we've been looking at the market about 40% of our low risk of patients are low risk. So of all treated patients about 40% low risk about half of those are bicuspid. And we have a bicuspid study starting in low risk patients. So we're running through that now.
Thanks. So I had one question for Mike, if I could, just a subject that's crossed over a few times between TAVR and CRM around Micron. We hear from clinicians their desire or hope that there might be some sort of PACEUR opportunity for 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.
In a prior life, Nina used to crawl the halls of the CRM business making all sorts of contacts. And so she's the one who's actually been working this. So I'll have her Yes.
No, we've been hearing that from physicians as well, this interest in having a short term temporary pacemaker. And so as I said often, and Mike and I have talked about, nobody knows more pacing than Medtronic. And so we our businesses are working together to address that 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 would just add, we're
just having that conversation 30 minutes ago.
So time line is TBD or something? Okay. And then on the And then maybe
you roll for Wink too in a different configuration as well.
And kind of bring everything together. So there's obviously great progress in stroke and mortality for both studies and we talked about PACER's durability still out there, but patient prosthesis mismatch and maybe lebithrombosis to a lesser degree, but 2 things that are sort of in the haven't fixed these, figure these things out yet sort of category. And I'd love Doctor. Padma, if you'd to give us some perspective on what you expect over the next 6, 12 months as we kind of expand this indication is do those get fixed, what have we learned and maybe what's next?
So, in terms of the precision mismatch, do you mean that how do we get further down with the self expanding technology or?
Yes, 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. But I guess maybe what do you see as the solution to that? And then what if anything is the next step on that?
That's a great question. So a couple of different ways to look at it. There was a whole session yesterday about with surgeons, talking about how they were going to get better gradients and there's certain surgical designs. And I don't know if anybody can talk about surgical design, maybe Peter can. There's surgical valves that actually are going to provide better gradients.
And there was a big play that we have to do maybe root enlargements in some patients. And then there was a nice discussion about does valves are specifically designed to do fracking and fracturing. So that was a whole animated discussion. We can't call it fracking anymore, but that whole idea of valve fracture. But I think that where the winner is, I mean, if I were going to pick the one thing with the human MSPDF, where the winner is in the self expanding technology, superannual self expanding technology, I think that data has been so consistent from the very beginning.
So I think that component of it is actually going to be a real advantage. And as we can accumulate the data out to 10 years, I think these grades are always going to be lower on the TAVR side, the self expanding TAVR side than on the surgery
side. Yes. You saw the series that Martin presented that actually the gradients were better with the surgical heart valves. While in our series it was reverse, the diver valve was much better than the surgical heart valve. So it was quite remarkable, I think, of his presentation.
Despite the fact that a lot of service put in Peter, really
the discussion post today is, okay, what prevents you from putting in a TAVR, right? The whole everything is shifted right now. It went from, okay, who gets a TAVR to who doesn't get a TAVR. And the pushback that's out there other than anatomical solutions, I think we have the answer on my custody and so forth is we go into this discussion of, okay, well, the 1 year data looks fantastic, but we don't know about 5 years, we don't know about 10 years. So you've heard that discussion at the podium today.
So maybe just touch on that because isn't that where the discussion heads after today? Okay, that's the last area of pushback is the durability question.
Yes. And I think Matt's making a great point is that the one component that we don't know about is we did LTI 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.
But just to editorialize about it, the bovine aneur valves are not the same thing as a supranure porcine valve. So let's just see how the data falls out. But I'm betting that the difference in design, the thinner, the longer and supranular, it should have less reasons to have lethal thrombosis than the other belt designs. And even if you look at the Makar data all the way through, maybe the point estimates are a little bit lower. So we can't really do it until we definitively see it.
But I think that there's reasons to think why that may be good. And we know that the valve durability is better. And we know from the New England Journal edits that we got away 10 years before we could say anything definitive about this stuff. So I hope we can just schedule this on the calendar 10 years from now, so we can all come back here to talk about whether that's right or not.
So And maybe to add to this sort of study that was presented in CRT that was mainly done by safety in heart valves, the incidence was 40% lethal thrombosis. There were only a few corovals in the study that didn't show any thrombosis. So there's speculation that it might be better than right now.
So we have to have something a year from now, right? We have to have something to come back for a year from now. So we'll all meet with the LTI sub studies. But 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 have good durability, quality of life for the long term. And those are the critical questions I left.
Okay, guys. I think we're coming up at the top of the hour at the bottom of the hour, I should say. One more question and maybe we'll go to Kristen.
Hi, thanks. It's Kristen Sheer from Barclays. I guess just wondering if you could comment on just how we should put into perspective all that we kind of have 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 RAPID study that can help to offset that over the near term. Just how do you think about the puts and takes here with all the news over the last week or so?
Well, certainly both of these studies year. On the other hand, I'm concerned about the paclitaxel impact and because of the replacement aspect of it in terms of lower procedure costs 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 and even though FDA has said what they've said, because 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. So we're going to see the market expand unfortunately over that time because of this. And 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.
So as you can imagine, this all came out Friday, so we're kind of working it. And I'm sure we'll have more to say on our next earnings call about what how to think about it, especially in the context of our plan for next year. Thank you very much. Thank you.