All right. Good afternoon. I'm Ryan Weispfenning, Vice President of Investor Relations for Medtronic. Thanks for joining us for our Structural Heart Investor Briefing here at the CRT Conference in Washington, D.C., and welcome to those joining us around the world on our webcast. Before we get started, go to the next slide here. I want to note that we could make some comments that may be considered forward-looking statements, and actual results might differ materially from those projected in any forward-looking statements. 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 the slide, and the slides that we are presenting today will be available on our website, which is investorrelations.medtronic.com.
Today's webcast event will last about an hour. Nina Goodheart, Vice President and General Manager of Structural Heart, will make some introductory remarks, and then Dr. Pieter Kapteyn, our Vice President and Chief Medical Officer of Structural Heart, will also make a few remarks. Following our presentation, Nina and Pieter will be happy to take your questions, and we plan to wrap up around 2:00 P.M. Eastern this afternoon. Nina, do you want to get us started?
Well, thank you all for joining us here. We don't usually have an investor discussion, I'll call it, at CRT. With ACC coming, thank you. With ACC coming and the focus of ACC, of course, we believe will be on our late-breaker trials, both our TYRX late-breaker and our Evolut low-risk late-breaker, we thought this would be a great opportunity to talk about things other than low risk. We've seen a huge amount of momentum in our TAVR program, we wanted to share a little bit with you about what we're seeing and why we're seeing it and be able to answer some of your questions. Clearly, with ACC just a couple of weeks away, we are not going to talk about low risk. I don't think any of you expect us to do that.
What we thought we would do is just walk you through the study design. I think as some of you may know, we have a Bayesian design, essentially, that allows us to take our two-year endpoint and take an interim look at that at one year. Professor Kapteyn will talk a little bit more about that. The design is just a little bit different than the traditional trial design, we thought it might be helpful just to walk you through that prior to you all getting to ACC. Essentially here, what you see is that, as I said, we're really seeing very, very strong momentum in the TAVR program, we think that's attributable to a couple of things.
First and foremost, the market that we operate in, about a $5 billion market, we're projecting by fiscal year 2022, growing in the mid-teens in that same timeframe, primarily driven by new indications, things like low risk, assuming the trials are positive, bicuspid, again, assuming our trials are positive, but also penetration into our current indications, our high risk and our intermediate risk indications. We've been seeing very strong performance from this valve. We've been very pleased with the performance of the valve. We've been talking a lot about our hemodynamics. We're going to talk a little bit about that today because we think that's been a primary driver for why we're seeing share gains. We'll talk about that.
We think that as we've educated physicians around the world about the benefits of this valve design and the hemodynamics that it offers, physicians are really seeing that as a benefit for their patients. Thus are using the CoreValve platform more and more across their spectrum of patients. We're seeing excellent procedural outcomes. We've got a strong TAVR solution, as you know. This valve is recapturable and repositionable, and that's a benefit that physicians have continued to see as they've gotten more and more experience with the Evolut program. Then we'll talk a little bit about our pipeline. As Omar mentioned in our last earnings call, and as Mike Coyle mentioned about CDG, this may be the strongest pipeline that we've seen at Medtronic in a really long time.
The same is true for our structural heart pipeline, extraordinarily strong, both on the TAVR side. We'll talk just a little bit about where we are with our Mitral program as well. We've talked a bit about share. I think in the last couple of calls, we've talked about our share growth for the Evolut program. This is something I think that we've been very pleased with, very proud of. We have a share position. I'm not sure everybody's always aware of this, but we have a share leadership position in almost all of our geographies, all of our regions, with the exception, of course, of some of the big ones, the U.S. and Japan in particular. We are seeing, however, share gain in those two geographies. Again, primarily driven by the benefit of the valve.
I know we've gotten questions about whether or not any of that share gain is coming from any price declines or any aggressive pricing programs that we've put in place. The answer to that is no. Our pricing has remained stable. We've been very pleased with the price stability of the market and of our program. The share gain is truly coming from the valve and the benefits that the valve provides. When we talk about why we're gaining share, we get a lot of questions about why we're gaining share. It's really primarily about the hemodynamics story that we've been talking about pretty extensively across the globe. Essentially, what we see here is that size matters and being big is a good thing here.
I'm going to let Professor Kapteyn talk you through what the hemodynamics are, why they matter, and why we're seeing such strong hemodynamics from the Evolut platform. As Ryan said, Professor Kapteyn is our Chief Medical Officer for our coronary and our Structural Heart business. He's a cardiac surgeon out of Rotterdam, has been a key thought leader in this space for a very long time. I won't say how long, but a very long time. We were ecstatic when Professor Kapteyn joined us in Medtronic Structural Heart and Coronary group. Why don't I let you walk through that, Pieter?
Well, thank you very much, Nina. Thank you all for joining us here for this meeting. Actually, it's an incredible journey. If I think back in November 2005, we did the first CoreValve implant in my center, in the Erasmus Medical Center in Rotterdam. At that time, it was a really collaboration between surgeon cardiologists. We went on bypass. We used a heart-lung machine to implant the first valves. The first three were using a heart-lung machine. We did two with just left heart bypass, and we also figured out that you can do it even without rapid pacing. If you think back, 2005, and where we are today, it's an incredible journey. Now we're doing those implants just on the local anesthesia. The patient is fully awake. Of course, the valve has changed as well.
It has been better performance what we see nowadays. As Nina mentioned, I'm a cardiac surgeon by training. As a cardiac surgeon, we know very well about the issue of patient-prosthesis mismatch. That actually means that if you put a valve in a patient where the orifice area is actually a little bit small, on the small side. Of course, what we want to do, we want to relieve aortic stenosis that a patient has. The area where the blood can go through the valve is too small. If you implant a valve that is too small, then you don't really gain a lot for the patients. I think the beauty of now is what we have seen now with Evolut R and Evolut PRO, that we see this great hemodynamic performance of the valve.
A larger EOA actually means that you have more area, so that the blood can go from the left side of the heart towards the aorta and then to the rest of the body. That means also that the work for the left ventricle is less. What you see also, that you get better remodeling of the left ventricle, and that, especially for long-term follow-up, is important. In surgical data, we have already shown that actually, if you have a patient-prosthesis mismatch, so if the valve is too small for that particular patient, that has an effect on long-term outcome. Mortality even is higher in patients that have severe patient-prosthesis mismatch compared to moderate or no patient-prosthesis mismatch. Actually, what you see here on the graph is that the smaller the area gets, the higher the gradient. Of course, we're always concerned about gradients.
You see a gradient with an aortic stenosis, you may also get a gradient when your valve is actually too small for that particular patient. A larger EOA is important. We were figuring out with our superannular valve that maybe we have a better EOA compared to some of our competitors. We were also very pleased, actually, with data that was published by an independent group, by Becky Hahn, who's a very respected echocardiographer from Columbia, that they published the data. They used the data from both PARTNER trial and from our trials, to see what the hemodynamic performance was of our valve compared to SAPIEN. What you see consistently over the different sizes of the valve, actually, that the EOA, as you can see here on the upper one, is better. Evolut R has consistently a better effective orifice area compared to SAPIEN.
That results in a lower gradient with Evolut R and Evolut PRO compared to the SAPIEN heart valve. Now, what does this mean for patients? You have a better effective orifice area. Your gradient is lower, so your hemodynamic performance of your valve is better. Does that really translate in a hard endpoint? Well, it does. Howie Herrmann from Philadelphia has published the data to show that actually there is an impact, also in transcatheter heart valve on that hard endpoint as mortality. As you can see here in this graph here, you see that if you have severe patient-prosthesis mismatch compared to moderate prosthesis mismatch or no mismatch at all, that actually your mortality is higher. I think this has resonated very well now with clinicians in the U.S.
If you implant a valve in a patient that actually needs a long-term follow-up, that needs to live much longer than, let's say, the 85-year-old, it's important to consider the patient-prosthesis mismatch and that you have a valve that performs very well. I think that is really the beauty of the new platform that the hemodynamic performance is so great. Having said that, we have done a lot of studies to show that our valves have performed well. It started already with the NOTION trial. The NOTION trial is actually investigator-initiated study out of Denmark by Professor Søndergaard from Copenhagen. The monitoring process, the analysis of the trial was all done and supported by Medtronic.
It was already published in 2013, actually, in a kind of all-comer study with a lot of low-risk patients included in the study, where we showed that actually the patient did very well with the TAVR device. The study has been followed up to 7 years, and we see also still that there's a great result with TAVR. There's no difference with surgical AVR. This is really a mostly low-risk patient population. When this study was being performed in Europe was a little bit ahead, of course, compared to the U.S. In the U.S., we started with the EXTREME and high-risk trial, randomized trial, a 1-year endpoint, and then followed by the intermediate-risk trial, which we also called SURTAVI.
A global TAVR trial versus surgical AVR randomized trial, a 1-year endpoint, and those patients will be followed up to 10 years. Both the surgical arm and the transcatheter arm will be followed that long. Now, of course, we're all waiting for what the low-risk trial will show us at ACC. That is in 2 weeks from now. That will be presented there. Besides those trials, we also have the registries, which are extremely important as well. You see here at the bottom of the slide 4 different registries, expanded use, a U.S. single arm study, 5-year follow-up on patients with a higher surgical risk. We have the FORWARD real-world registry, 1-year follow-up, multicenter European data on Evolut R. We have the FORWARD PRO registry, a real-world registry again, 2-year follow-up on patient with all surgical risks, so this includes all patients.
We have the bicuspid study, which is, of course, a little different than just risk profiles. This is really focusing on a special anatomical subset of patients. As you see, we put a lot of effort in those trials, generating evidence. The good thing is also we follow all those patients, and we also publish this data. That sometimes not all our competitors do this the same. Yep. Yeah. Low risk, what we see that low-risk patients, the incidence of bicuspid valve is much higher than in the elderly patients. If we move towards a lower-risk patient population, patients will probably also be younger, and they will also have more bicuspid valves. Therefore, it's important to generate evidence that you can also treat patients with bicuspid valves.
In general, what we see is that patients who have three leaflets, which is hopefully everybody in room has three leaflets in their aortic valve. Bicuspid patients have only two leaflets. What you see is that actually it's a kind of congenital malformation of the aortic valve, that they are more prone to calcification. They get more often stenosis. Not only that they get stenosis, the calcium is also not distributed symmetrically. They have sometimes big piece of calcium just on one side of the aortic valve. Therefore, it might be more challenging to treat those patients with bicuspid valves. Therefore, we think it's important to generate that data as well, that our device also works in patients with bicuspid valve. Yep, great. Just A question? Yep. Yeah. Right. There are challenging and less challenging bicuspid cases. Absolutely.
You have bicuspid cases where you hardly see. Normally what you see in bicuspid cases is also that you see the start of where the third leaflet should have been. Those probably are a little bit easier than if you don't see any indication where actually Mother Nature would have thought that the third leaflet would have begun. The majority of patients, fortunately enough, they have good anatomy where you always see kind of what we call a raphe. The start of where the third leaflet should have been. We think that from the 50%, a lot of those patients can be treated with transcatheter heart valves. To find out the right methodology to do it and the sizing methodology, that's why we do those studies. If we think about low risk, we also want to look back a little bit to SURTAVI.
Maybe you remember that the SURTAVI trial that we presented had what we call a Bayesian analysis. Bayesian is this kind of statistical methodology where you can use data to predict also outcome. You can actually have an earlier look than waiting until all patients have completed their follow-up. That's the beauty of Bayesian analysis. You still have the same number of patients that you originally estimated that you should need for a trial. It doesn't mean that your sample size will get smaller, but it allows you to take an earlier look at your data and to predict actually what the two-year outcome will be for all your patients. We had a similar statistical technique, Bayesian analysis, for our SURTAVI trial.
Of course, what we did, we presented it, the Bayesian analysis, and that was published in the New England Journal of Medicine and which actually also the FDA has given guidance on, that we maybe use Bayesian analysis more often. We also followed those patients until we had the complete three-year follow-up. Of course, what was very interesting to see, did our Bayesian analysis predict what we saw in real life, you could say? Until we had the complete follow-up. These are the two curves. You see here, TAVR is the yellow line and surgical AVR is the blue line. This is the interim analysis from SURTAVI. This is what you could call the Bayesian analysis, and this is what we call in statistical terms the frequentist analysis. The real follow-up of two years.
Actually what you see is actually there's hardly any difference between the two. The Bayesian analysis predicted exactly what the frequentist analysis showed as well. That's important to keep in mind because now if we go to the next slide, you will see this is our low-risk trial design. The low risk is a heart team evaluation, again. What we also had in the previous trial, surgeon and cardiologists had to agree that this patient could be randomized because both should be able to perform either surgery or transcatheter heart valve implantation. When the heart team had confirmed that they thought the patient could be randomized, there was a screening committee that would check whether all the inclusion/exclusion criteria were met.
Once they were met, the patient was randomized. The patient was randomized either to transcatheter aortic valve replacement or surgical aortic valve replacement. We allowed patients to also be revascularized. You see in the TAVR arm, we have two groups, TAVR only or TAVR plus PCI. In the surgical group, we have surgical valve replacement only or surgical aortic valve replacement plus coronary revascularization. We're all looking forward at ACC, the late breaking trial session. It's at 8:15 A.M., early in the morning on Sunday in the main hall, the great tent, session 404. We will present our data at the same time Edwards will present the data. There will be followed by a discussion. We're looking forward. Probably you will all be there in New Orleans and have the discussion then. Good? Yeah, question. Thank you.
Rick Wise. Just a couple of questions on the data we're going to see at ACC. How much of the low-risk trial was Evolut versus Pro, and is there some way to talk about that? As we try to get ready to assess the pacer rate impact, I assume it's going to be less with Pro.
Yeah. Unfortunately, we're not allowed to show those data.
Moving right along.
Yeah. All the data is actually from the low-risk. That's why we had this meeting here, to give you a little bit of an update what the design was.
Jesus. I know.
Yeah.
I'll ask a today question. You talked about hemodynamics and the importance of it, and I've heard that over the last couple of days here. I'm not sure what I'm exactly asking, but if I reflect on smaller orifice and the hemodynamics are obviously better with larger, what's it mean for your smaller size implants? Does this say something about implanting, the choosing to implant a 23-millimeter valve, and are there implications there that we should be thinking about going forward given the hemodynamic story?
Yeah. I think especially in the lower sizes, the smaller sizes, we have a major advantage over SAPIEN. There are even people that called and said this morning it's criminal to implant a 20 or 23 SAPIEN heart valve nowadays if you look at the data, the hemodynamic performance of Evolut. You really end up with a higher gradient, and especially in lower SAPIEN, you should think that if you have a gradient at rest of 15 or 20 millimeters of mercury, when you exercise, that gradient goes up to 40, 50, or 60 millimeters of mercury. You have more cardiac output, so your heart is pumping more blood. If you have an orifice that is too small, your gradient becomes more higher. That has an impact on your left side of the heart or your muscle.
You get less what we call left ventricular regression, which means that your heart goes back to the normal state, like hopefully we all have here in the room. It has an impact on long-term mortality, especially in young patients because they exercise. They go shopping. They walk the stairs, et cetera. Every time that you do that, your gradient goes up. It goes up to 30 or 40. That has a major impact.
Just one other topic and I'll be done. Coronary access seems to be another very critical topic, just as important as hemodynamics. Maybe talk about the Evolut PRO and just how you all stack up in your opinion and what you're doing to make sure that subsequent generation valves have that access.
Yeah. The coronary access, of course, is something because if you have a larger frame, people are afraid that your coronary access might be an issue. It's also not zero with SAPIEN because the stent of the SAPIEN valve may be just at the coronary ostium as well and may also have a more difficult access. What we have learned also from a lot of cardiologists that have implanted a lot of valves and said there are special techniques to get better coronary access. What we will also focus on to learn those techniques to other physicians as well so that they can have a better access to the coronary ostium. Of course, Nina will talk a little bit about our platforms and where we are going with the next generation. She will address that issue as well with coronary ostium.
The other thing what I want to say is that sometimes, of course, it's very intuitive to think coronary access might be the problem. If you see how many patients actually need repeat revascularization after an aortic valve implantation, it's a very low percentage actually. We know that from surgical aortic valve replacements, which are mimicking the low-risk trial population, there are not that many patients that need during a follow-up a repeat revascularization. Oh, sorry. Okay. First Nina, and then we will, yeah, answer all the questions. Good. Yeah.
Thanks. As we think about the platforms and the programs that we've got coming to address some of the unmet needs in the market, you're all familiar with the current Evolut PRO and EnVeo PRO platforms that we currently have on the market. That's what's giving us this really strong hemodynamic performance that Pieter has talked about. Our next program coming forward is what we are calling Evolut PRO. That will do a couple of things for us. As you know, we have a wrap or a skirt on almost all of our valves that's led to some of this increased and improved performance. Physicians have told us that they are very pleased with the performance that the skirt delivers. We did not have that skirt or that wrap on the 34 or larger size valve.
Physicians have told us that they would be interested in utilizing that valve more if it had that skirt. We will be wrapping the 34 in this program, and that will be coming somewhere in the mid-fiscal year 2020 range. We've also taken our profile down. If you remember when we started all these valves, we took the profile up by two. We're now bringing that down to a 14 French size across the platform, so we'll take down the profile. As we've talked about before, we've made an acquisition of an expandable sheath, something physicians have told us that they liked. That will be a 12 French sheath that will also be coming in that mid-fiscal year 2020 timeframe. Program coming after that, we have not yet set timing for that, is a program we're calling Evolut FX.
I don't think that we talked about that specifically here. It's a strong program for us in development. That's where we're really looking at improving the positioning of the valve and providing a little bit more visualization. Putting some radiopaque markers on so that there's a little bit more of clarity when you're looking at where you've positioned that valve, and that's something that physicians have also told us they're looking at. We're looking forward to bringing that program into the market. Next comes what I would call our next transformative program. We have called that Horizon. You will never see a product called Horizon, but that's the program name. That's where we're looking at things, to your point about coronary access, whether or not we can start to build valves that start to meet some of those needs.
We're looking at things like taking the frame size down a little bit to provide better access to the coronaries. We're looking at things like widening the windows a little bit to, again, potentially provide more access to the coronaries. That's a program I think we're pretty excited about currently in development, and we'll be talking more about that as we go forward. I thought I'd talk just a little bit about mitral while you're all here. You all know where we are with mitral. I have talked, I think, pretty publicly about our belief that we're going to need a toolbox of approaches, if you will, as we think about mitral. Mitral being much more complicated than the aortic space. I think you've all seen that.
We've indexed down hard, as you know, on replacement. We have our current APOLLO program running, our Intrepid valve performing well. After TCT, as you know, we saw the COAPT results. I think everybody was ecstatic about those COAPT results. We were very pleased because I think what that told us was a couple of things. One is you could treat these patients who weren't really sure prior to COAPT, and that we could treat them with device therapy, which essentially opens up, I think, a whole new market. Discussions around repair and replacement. Our feeling has always been that if you can reduce MR, that's good. If we could eliminate it, that would be better, and thus has been our focus on replacement. The trial's continuing to run.
We've gotten some questions as to whether or not we've seen any changes in enrollments, declines in enrollments after COAPT. I have to say we haven't. Physicians have remained really enthusiastic about this program. We're continuing to see that enrollment. These are hard trials to enroll. They're early trials. We saw that with COAPT, as you know, a very long trial to enroll. We're pretty pleased with where we're going. We've had discussions with FDA on this program. They're also pleased with where this is going. We'll continue to move forward. In terms of repair, we're also looking very strongly at repair. We do have an investment that we've made in repair. That program's going very well. We're looking at some of the unmet needs in the repair space. Specifically, we think about things like ease of use. We think about lifetime management.
If you remember with MitraClip, a lot of times, physicians are starting to see failed MitraClips come back. Once a MitraClip fails, there's no place else to go. You can't do a replacement in a failed MitraClip. We're looking at providing options that give physicians and patients more options once they have a mitral repair. We think the program we have is pretty differentiated. We're not going to talk too much about it until we're a little bit further along. We're excited and enthusiastic about what we see. We're going to continue to move that program forward. What you'll see from us coming forward is both replacement and repair technology solutions. I think with that, we'll close out here. When we think about structural heart, at least for Medtronic, we think about solutions for all four valves.
You know we have a strong congenital program. Our Harmony trial is continuing to run. That will be closing out very quickly. Our congenital physicians are really pleased about having a new option. We've talked about where we are in TAVR. We're excited to see what the low-risk results will look like. I think we're pretty excited about the fact that we started so much later than our competitor in terms of getting that trial up and running. To be on the same podium, I think is a tribute to both our clinical team and our investigators. I think that'll be great for the clinical community to be able to see both of these trials coming forward as we move forward. With that, oh my goodness. Are there any questions?
Go to Bruce.
Oh, sorry.
Sorry. Just a quick question. Could you explain what you're going to be putting on at ACC in terms of the Bayesian analysis or the final frequentist analysis? What's going to be presented there? Just to clarify.
ACC is the Bayesian analysis.
Would you say what percentage of patients or?
Currently, we cannot say that. Well, you will see. It allows us to present data. That's the only thing we can say.
Chris Hitov from SunTrust. One definitional question on the protocol. Is the rule-out for all bicuspids inclusive acquired bicuspids or just congenital bicuspids? The prior trials were all really congenital bicuspids for the rule-out, I think.
It's hard to distinguish whether a bicuspid valve is congenital or acquired. Acquired means actually fusion of leaflets. Those are actually considered tricuspid valves, because you can clearly see, and as a surgeon, I can tell you that you can clearly see three leaflets and three commissures.
Okay.
the congenital ones that we identify are mostly, that's on CT scans, the congenital ones. We would like to get 100% true bicuspid valves.
my second follow-up is on, you brought up the EOA as being an important success factor. You spoke to the coronary access, but there's also when dealing with long-term implants, pacemaker rates, ability to expand in the face of heavy calcification, and maybe leaflet thrombosis, where you may, in fact, have an advantage. Could you just comment on those three other elements?
to start with the last one, I think the leaflet thrombosis, of course, it is very speculative what I say, but we think that better hemodynamics, the supra-annular performance of our valve, that you get better washing effect of the leaflets and that valve leaflet thrombosis might be lower with our platform. That's the other thing. You talk about pacemakers, of course, that is something where we have a close look at. We see still a wide range of pacemaker implantation. We see centers that have a pacemaker implantation rate as low as the surgery, and we see that have higher. Currently we're doing also some studies to understand better what is now the predictor for conduction disturbance. Once we know that better, we hopefully can drive that down further. Completely agree with you that the lower, the better it is.
we see already low rates in the 5%, 6%, 7% in some centers.
The expansive force.
Yeah, the expansive force. We think that with the self-expandable valve, you have enough radial strength to really treat bicuspid patients. It's not that we have zero experience. Actually, in Europe, a lot of patients with bicuspid valves are currently treated. It's, of course, different, the environment in the U.S. where you have to get FDA approval to get an indication for it. In Europe, lots of patients with bicuspid valves are successfully treated. Yeah.
Thanks. Joshua Jennings from Cowen. One, can you size that up for us in terms of the percentage of small annulus patients that get surgical valves or open surgery historically? Is that where you're really seeing the shared gains take place is in that segment?
Yeah. Again, of course, I would love to answer your question directly of how many patients were in our low-risk population with a small size. I cannot tell you at this moment what that percentage actually is. Of course, there are lots of patients. It depends on the population we're looking at. Roughly it will be about one-third of the patients that have a small size. With the low-risk data presentation, look at those 21s and the 20, 23s, et cetera, how many are-
Across high risk-
Yeah
intermediate risk, a little over a third.
Yes.
Great. Then just a-
I think we probably can make a comment because share-wise, it hasn't been on that five for.
Yeah.
Because we haven't had on the 34-
Right. Very quick
Getting that skirt on the 34.
I would say two things there. Mike's absolutely right. We have seen significant share gains as physicians, whether they are strong Medtronic users or they use competitive valves, really understanding the benefits of the hemodynamics in those small annulus patients. Even physicians who historically have not been strong CoreValve users, as this data continues to come out, have moved their small annulus patients to CoreValve. As they are getting more experience with that, they're seeing the benefits of those hemodynamics. We're now seeing that beyond just those small annulus patients. To Mike's point, as we skirt the 34 and then start to see some of the improved performance there, we're relatively optimistic that we'll see that as well.
The hemodynamics story, to your point, absolutely playing well in the small annulus, but it's sort of creeping across the rest of the continuum.
Great. Just a question on the Low Risk TAVR trial design. Can you just remind us, in terms of the decision not to include rehospitalizations versus the PARTNER 3 design, then any thoughts, high level, on the LRT data that was just presented today, particularly the hospitalization rate? Thanks a lot.
Yeah. Excellent point. Actually, across all our trials, we had mortality of stroke as endpoint. We kept that also for the low-risk patient population. What I really urge you to look at the repeat hospitalization also at ACC and the discussion around it, because there are different repeat hospitalizations. What is exactly the definition and how to adjudicate repeat hospitalization is actually not easy. It's a much softer endpoint. You can have repeat hospitalization for all causes. You can say, well, we just focus on repeat hospitalization for valve reasons, or you can say for heart failure, or as you can say, repeat hospitalization. There are many different definitions. I think that makes it hard to compare if you have repeat hospitalization in your endpoint to compare one study versus another one.
Therefore, we focus really on mortality and stroke, which matters of course very much for patients. They want to stay alive and want to stay happy. That's across all our trials. Therefore we choose that. Of course, we have also secondary endpoints, so we also report other endpoints as well, including repeat hospitalization. But please pay take attention to how it is defined, because that will be different. Ron's data. Actually, I think it gives us a good feeling with the data that he presented. I think you know, of course, our trials is much larger sample size, so I think it's more robust. It's mostly SAPIEN data that he presented. I think it's heading in the right direction. Yeah. It's a good outcome, I think.
It's really a good alternative, what he presented, compared to surgery. Yeah.
Ravi.
Thanks. Ravi Misra from JPMorgan. Two questions, maybe one TAVR, one TMVR. With TAVR, you have some new types of self-expanding valves coming out in Europe and moving into the U.S., and some new competitors coming in. Can you give us your thoughts on, A, how you feel you're positioned versus those competitors, and then, B, what you can do to hopefully maintain and prevent loss of share?
I think we're going to remain focused on the story that we've been telling and the data that we've been generating around this whole, again, this whole hemodynamic story and the benefits that the PRO valve has. We're seeing competitors come into the market. We are not yet seeing a lot of traction in Europe, so we'll continue to watch that. We're expecting the same kind of entry into the U.S. I think that physicians are going to evaluate these on valve performance. When I look at the performance of the PRO valve right now, we're feeling very confident about that. Of course, we'll continue to watch it, but we're feeling good about where we are and the story that we're continuing to tell.
Do you think pricing's going to come down in the U.S. or Europe with new entrants?
I think if we look at any market, the more entrants you get, we'll see some pricing pressure. This has been a pretty price-stable market. It's been a pretty price-disciplined market. I think we'll look to maintain that as much as we can, and we'll continue to watch and see what our competitors do.
On TMVR and the Intrepid program and your repair program. Intrepid, can you remind us where you stand in terms of getting transfemoral access, how far out that is, and is it a reality? On the repair side, some of your competitors are going different flavors of repair.
Yeah.
Can you give us any sense of which type of repair device you're going at, and are you going after multiple options?
Yeah. On the Intrepid side, remind me of your question again, the first half of it.
Where you stand in terms of transfemoral access.
Yeah. Our belief is that in order to be successful, we're going to have a transfemoral or transfemoral system. We've set our focus very specifically on the ability to develop a transfemoral system. I think we've got really good line of sight to that now. We've got a strong engineering team working on that. Our goal is absolutely to come to market with a transfemoral system. Repair. I'm not going to talk a lot about repair because as I said, we're feeling really good about what we have right now. We're really focusing again on things like ease of use and lifetime management of our repair technology. I think it's moving at a good speed, so we're comfortable with that. This is early times in this whole market, and I think we're seeing a lot of things coming.
We're seeing some things fail very early, as you would expect. We'll see some things come a little further and potentially fail. This is a market we're just going to have to watch really closely.
I'll just add, just to maybe help Nina's comments, part of the reason we're being so vague and not sharing more on the repairs is because we do have approach that's different than some of the other approaches you've seen out there. We'd want to keep it as close to the vest as possible for as long as possible.
Yeah.
Thank you, Jason Mills, Canaccord Genuity. Thank you for doing this meeting. On the mitral side, Nina, first, I appreciate at this point it seems silly to try to ascertain whether or not enrollment's accelerating or decelerating.
Yeah.
What we have heard, though, is it's very hard to enroll that surgical.
Yeah.
Both your trial and others. Maybe talk about that, whether that's true and what you're seeing, and maybe what that does to inform how you'll design trials in the future as it relates to mitral.
Yeah.
The FDA, I know, they're holding town halls today and other days on structural heart. They continue to do that. Do you think it's possible we're going to see for replacement devices, getting away from this randomization to surgery? It's not done that much.
Right.
I'm wondering what your thoughts are on that.
I'll ask Eric Vang in the back to comment. He's the director of our clinical program. It's a slow enrolling trial. We expected it to be a slow enrolling trial. It's, again, early days. We saw COAPT, a very slow enrolling trial. I'm pleased that we're enrolling faster than that, which is good. We continue to have discussions with FDA about the design of the trial, to see whether or not there are any protocol adjustments that we might want to make. We may make some small protocol adjustments as we go forward, but we'll be able to disclose that, I think, after we continue to have FDA discussions. I don't know, Eric, if there's anything you want to add?
Seems to be a lot of unanswered questions, as we work with FDA on the current APOLLO trial or as we look at alternatives, certainly FDA is open to the designs and the control arms, primarily because there is not a standard of care for these patients. As we see it today, we still have an option forward with the current trial design, but we're definitely going to continue to explore opportunities moving forward.
Just as a follow-up to that, on the mitral side, appreciate that you don't want to disclose too much about your internal programs. Will, over the next three years, your mitral program be developed both via internal programs and M&A, in your view? Is that a fairly high probability, sort of going both ways?
I would say yes.
Matt Miksic from Credit Suisse. I had a couple of follow-ups. One, just on expectations, doctor, if you could, on the-
When we see the inflection or when we see the sort of uptake, what this looks like in the community, assuming that we get positive data in a couple of weeks, and assuming that approval comes for both valves by the end of the year or something like that. Help us understand maybe that process and maybe how it might be different from the process around intermediate risk. I have one follow-up.
Yeah. I think with the low risk, I think it will also be important to look at the baseline characteristic, what is the age of the population. I think when we show that low risk is non-inferior to surgery, what is then the reason to do surgical AVR in a certain type of patients? I think when we have proven this, the only question that remains is the durability. Where people may be a little bit concerned about, have you proven it? On the other hand, surgical data is also limited on durability. We have always claimed that we had a 13, 14, 15-year follow-up, but it's not based on echo data. It's based on reoperation-free data. Everybody currently understands that actually there's a shortcoming as well in the surgical literature.
I think that points to the fact that durability might be an issue, might be a concern, but actually we just have to wait for a longer follow-up. The good thing about the NOTION trial, 7-year follow-up actually showed that TAVR had a better durability than surgical AVR. That takes away a lot of the concerns that people currently have on the durability of transcatheter heart valves.
Absolutely.
We have a long-term follow-up now already, and there will be patients up to 10-year follow-up not long from now.
Just to push on the inflection. Does this take 6 months in the community? Does it take middle of next calendar year, early next calendar year? When would you expect an uptick?
Of course, everybody will be aware, I guess, after the ACC presentation, what the results are. People are already anticipating what am I going to do once we get approval. I think the uptick might be pretty fast after that. I think also that patients will ask for it. Patient will hear this as well. There might be articles in The New York Times, maybe those trials will also be publishing. I don't know, but journalists may pick it up. The patient will pick it up and will go to their physician and say, "Can I not have a transcatheter aortic valve instead of surgery?
I think we're seeing that shared decision-making is going to become a bigger issue in low risk, assuming again that the trials are positive. Once patients start to realize that there are options, and although physicians hate when we say this, a patient walks in and says, "I don't want to have my chest cracked open. I know that there's another alternative." Physicians are telling us that they are anticipating longer discussions, and patients really coming in with requests for TAVR versus surgery. They're going to have to take that into account.
What I would say, I'm also chief medical officer for cardiac surgery. What I'd say to the surgeons that we have this discussion now is that we should focus on those patients that still need a surgical aortic valve replacement. That means those with extensive coronary disease, where you need a coronary bypass operation at the same time. Those patients with double or triple valves, and those patients that also need a replacement of the ascending aorta. That is a little bit more difficult type of operation. We need those surgeons. I think as surgeons, we should focus on those type of patients and how to educate the next generation of surgeons. There will still be plenty of surgery that is needed. There will be patients, for example, with a transcatheter aortic valve that develop endocarditis.
It's the same rate as with surgical endocarditis, but the option is not replacing the transcatheter. You have to take it out. Surgeries are still needed in the future.
Mike, did you want to say something?
Yeah, I would just say for those that were for this, I was in the room for Waksman's presentation. You heard one of the questions from the panel. Just, okay, this is great. You're showing us 30-day and one-year data, but we're talking about patients that are going to live 10 to hopefully 20 years. What we're going to see at ACC is going to be one year and two-year projected data, right?
Yes.
For surgeons, it still doesn't answer that question. Because if we go into this dynamic where patients are asking, say, "Well, I don't want to have surgery. I read the USA Today article, and I saw it on Good Morning America, and I don't want to have to crack my chest anymore." The conversation starts to shift where it's okay, well, if the patients are saying, I don't want to have surgery anymore, and I have that transcatheter valve, the discussion shifts to okay, well, we don't have 10-year follow-ups on these valves. Which valve do I feel most comfortable putting in a patient that I believe is going to last for 10-plus years? That's part of what our messaging has been, particularly post the papers that came out last summer. I know that's going to be covered in the symposium tonight.
That's a Medtronic-sponsored symposium part of it. There's Dr. Herrmann has a session, I think at 3:30 P.M. today on mismatch. Maybe just spend a minute, Pieter, on just coming back to say why when valves fail, why do they fail? I think educating people on that, because ultimately, if we're talking about patients asking for TAVR and physicians making decisions based on which valve they are comfortable is going to still be working a decade out.
Yeah.
The question of why might a valve fail is an important one.
Good point because when I discussed the patient- prosthesis mismatch issue, I pointed out to mortality. In surgical literature, we also have shown that if you have patient- prosthesis mismatch, that also has an impact on durability. The better your hemodynamic performance of your valve is, the longer it will last as well. Those are important factors to take into account. Why would a heart valve fail at a certain moment? It will mostly calcify, or you may get an infection. Infection is something you almost cannot prevent. We always tell patients, you have to go to your dentist. You have to be careful with your valve. If you get a wound, it should be cleaned, et cetera. Those kind of things to lower the infection rate and lower endocarditis rate. If the valve calcifies, that's something you can hardly prevent.
The only thing is, we think that if you have a valve that opens symmetrically, if the forces are distributed over all three leaflets equally, that the valve will last longer. That's something we have mimicked in our laboratory in Orange County, where we put the valves in, and if you have the valve that is not completely circular at the base where you implant it's still circular at the level where the valve leaflets function. That is because of the supra-annular design. Then your three leaflets open symmetrically, and the stress on the leaflet is less than if just one leaflet gets a lot of blood instead of the other, all three at the same time.
Yeah. Just follow up, if that's okay, on the NCD. Just your thoughts, business planning on expectations for the NCD and the MS.
That's our knowledge. We'll see the NCD at the end of this month. I think the 27th is the date that has been talked about. I believe that we will see volume requirements less than what the societies initially proposed, slightly more than what we currently have. We've been aligned with the societies that at this point, we still need some volume requirements until there's an outcome that we can tie this to. I think it's going to be in align with everything we've been saying since the start of the NCD process.
Bruce.
One of the funny things that happened on Saturday is they showed the relationship between SAVR outcomes and volume, and they were indistinguishable from the TAVR outcomes and volume. It made the whole NCD seem a little ridiculous. I wonder if you'd comment on that. Also, secondarily on, let's say, both trials, when you combine them at ACC, show just strong trends on hard outcomes. What does that mean for the SAVR patients over 65? Will doctors have to tell them that TAVR is a very legitimate alternative?
I think to start with the last point, yes. I think, if it's a hard endpoint like mortality, which is different, I think, yeah, doctors have to tell that, be honest to their patients. Because the patient may ask, "So what is the benefit then of surgery?" I think for a surgeon, it's hard to explain at that moment, what is then the benefit. I think yeah, rightfully so, they have to tell it. Your first point-
On the-
Yeah.
Apply the same rules to surgery.
Yeah. Right. Exactly.
Yeah.
Yes, for sure.
You were saying that.
Suppose that there will be a three or four% difference in mortality, then maybe you have to shift. That's hard, of course, but yeah. Rightfully so.
You're talking to a surgeon, it's hard.
Yeah. You're right. It's hard for me to express myself in.
I think you're right
You're absolutely right. Yeah.
Go ahead, Chris.
Just one more question from me. This morning, Dr. Goffi, we saw your friends in Rotterdam. I assume they're your friends.
Yeah. Sure.
Do a live procedure and using the Sentinel device. They were stressing the importance of protection. They showed us the clots.
Yeah
there are several docs on the panel that basically said One said, "I do every single case with protection.
Yeah.
Another said, "No way," because it's so expensive. What are your evolving thoughts about the importance of this? How should we think about it as, gosh, it sounds important, and yet stroke rates are low.
Right. I think.
What does the future hold?
I think you just hit the conundrum right on the head. Right. The stroke rates have been very low, and so physicians will point to that. There is, I think, an emotional reaction with that device when you see debris that is pulled. Right. The data was negative, as you all know. It is hard to believe that somebody is going to do a stroke outcome trial because they are so big and they take so long. Even our neurologists, as you know, we have a strong stroke program at Medtronic, and I talked to our neurologists about this, and they will say, "We want to see data," but it is hard to argue with taking that from the brain, not having it go to the brain. That has to be a good thing. We are not sure if you could do just a little bit of damage with that device.
I think that the jury is still out on that. I think overall, what physicians have been telling us is that intuitively, you want to do everything you can to protect the patient from stroke. One stroke is a stroke too many. They do not see a lot. Their feeling is that the Sentinel is expensive. Boston will figure that out. From an overall embolic protection, I think we are going to see growth in that. I do. I think we.
What was the protection?
Well, a stroke is devastating when you are 90. I do not want to put quality of life on people's ages, but a stroke at 65 or 75 could potentially be considered more devastating. There may be an opportunity there.
Christine Zhao from Barclays. I was just wondering if you could maybe just share your thoughts on the total size of the mitral opportunity, both repair, replacement. I was struck that your market estimates of $4 billion by FY 2027 weren't very different from what you guys had talked about this past summer, despite the COAPT trial results. Just trying to think about how you guys still view the split between replacement and repair, because it seems like some other people are rethinking, it sounds like you might be too, what repair might be as a percentage.
I don't think we really know yet. I think it's a market that we continue to watch and to size, so we're showing you what we're looking at right now. We're continuing to watch MitraClip. There's no approval yet, there's no reimbursement yet. I don't think we really know what's going to happen there. We'll watch that carefully, and we'll continue to size if we think that a change is warranted.
I think the beauty of COAPT was that it shows that reduction of MR works.
Yes.
You have a better survival.
You could say with the repair device, you will reduce MR but not completely eliminate it. Maybe, with the replacement, if you completely eliminate MR, maybe you get a better survival. Therefore, what Nina said, we don't know actually, which market, and how big it will be. With degenerative mitral regurgitation, so far it has always been repair as a preferred approach. Maybe replacement has also worked out very well.
Still a lot to learn with mitral market.
What's been the main challenge in terms of moving the Intrepid device transseptal? Because you guys had thought about getting it in some sort of program by the back half of fiscal 2019. I don't think I heard from you today a specific timeline for that. What's been the main challenge? Is it just you could do it, but you're trying to size it much smaller, or?
I think we're looking at two things. We're looking at making it transseptal, and we're looking at making the system smaller, and we're looking to do that together. I don't know that a 43 transseptal system is going to be very helpful to the market. We're looking to do both of those things at the same time, and there are engineering challenges that get raised when you do that. I think we're working through them. I think the team's feeling pretty good about their ability to get there.
Year?
For first in humans?
Yeah.
Say within the next 12-18 months.
Okay. Thank you.
One more question here before we wrap up, Adam.
Adam Maeder, Wells Fargo, thanks for taking the question. I wanted to follow up on the NCD commentary. Any sense for how much greater you think the TAVR requirements will be versus the current NCD? Just any thoughts on how that will impact TAVR volumes?
In terms of the volumes that will be required in the NCD?
Correct.
Everything that we're hearing is that it will be less than the 50 that the societies originally proposed, a little bit more than we currently have now. I'm guessing somewhere in that mid-20s range, but it's just conjecture on my part. We'll have to wait for the 27th to see what that looks like.
Great. Thank you, everyone.
Thank you.
Thank you.