Hello, hello, everyone. You know, good afternoon. And again, you know, thanks for being here, you know, for the what? The third time of the week, you know, together, which is great. What a busy week. You know, I want to start with, you know, I'm sure you remember, you know, a few years ago, as a company, we had a vision for TMTT. The vision of transforming lives, you know, for patients with mitral and tricuspid disease. And we said, you know, if you want to be successful, you know, we need a toolbox, you know, we need a portfolio. And, you know, this is what we did.
I am very pleased, you know, to report, you know, today that after, you know, many years of commitment, we made, you know, major progress with a very important milestone achieved across, you know, many, many things. First one is, you know, PASCAL in Japan. You know, PASCAL was approved in Europe, you know, for a long time, in the U.S. about a year ago, now in Japan. Being in Japan now, you know, we are, you know, present in the three largest, you know, geography. We are continuing to expand. The CE Mark of EVOQUE, super important. You know, physicians for a long time had only one therapy, a clip or PASCAL, you know, for tricuspid patient.
And now, you know, they will be able to learn more about, you know, what patient, you know, therapy. They will be able to treat even more patients. So truly, the CE Mark of EVOQUE is an important step toward having a toolbox, you know, for physicians. The completion of enrollment of SAPIEN M3 pivotal study also is very important. You know, more than 10 years with MitraClip, you know, a few years, you know, in Europe, you know, with PASCAL, but we know that, you know, a clip and a TEER device can treat only a very small number of patients. So again, here on the mitral side, you know, we are one step away from having a mitral replacement approved here. All of these, all of these technologies supported by evidence, which we know it is very important.
You know, we have been a pioneer in TAVR, and we know that we are leveraging our experience that, you know, made, you know, TAVR successful in TMTT. So now, you know, for today, let's focus on these, you know, two widely anticipated study, CLASP IID, one year, first of its kind, you know, comparing two devices, MitraClip and PASCAL for DMR patient and TRISCEND II. I am very proud about the trials, the data, proud about, you know, the many physicians that, you know, were part of this, commitment to evidence. Proud also the team that, you know, just completely embrace, you know, the vision. I'm sure you remember, you know, we said, you know, we need to have, you know, five pivotal study to be able to bring evidence to help, you know, physicians treat patients. So for the team, it was a big, big undertaking.
So today with us, you know, we have two of those physicians, Dr. Susheel Kodali from, who is the Director of Structural Heart and Valve Center at Columbia University, and Dr. Firas Zahr, Director of Interventional Cardiology at Oregon Health & Science University. It is a true privilege, you know, to have, you know, this kind of clinicians, academic physician, who are truly caring for patients and for advancing of the science. Also on stage is, Dr. Ted Feldman, who, before joining, you know, the TMTT about, you know, Ted, you know, five, five years ago, was a pioneer in interventional cardiology for more than 40 years. He has seen, you know, all, you know, the beginning, how difficult it is, you know, to make a technology a success and to bring, you know, this to many patients.
And finally, you know, also joining, you know, us today is Daveen Chopra, our Global Leader for TMTT. So with that, I'm going to let you know, Ted kick off, you know, this meeting. Ted?
Great. I want to spend just a minute, and are we gonna have slides? Do we finally Oh, great. Just a couple of slides, this slide totally to just hit a couple of the highlights of the two trials. So the CLASP IID trial we presented a year ago at this meeting, six-month results in 180 patients, and the primary outcome measure in that trial was MR reduction. And the reason that that trial was the basis for FDA approval is that we statistically made the assertion that those MR reduction results at six months would predict the twelve-month clinical outcomes. That was using a predictive probability or Bayesian statistical method. And our predictive probability that those six-month results would accurately predict twelve-month clinical outcomes a year ago was about 99%. So we were pretty confident about the way the results that you saw today would look.
In fact, the non-inferiority comparison for both safety and efficacy outcomes were borne out very clearly and with a lot more depth and a bigger population with the 12-month results. I would say, as importantly, we prospectively outlined a group of complex anatomy patients for a registry, so no comparative arm, but these were a group of patients who couldn't be randomized because of complex anatomy, who really had never been prospectively studied before. Today, we showed quite good results in that group as well, demonstrating that certainly we've been treating them for many, many years, but that there's a basis for that therapy.
For the TRISCEND II trial, similarly, we, a year ago, more than a year ago, presented single-arm data, and recently, just have in press in the European Heart Journal, one-year outcomes on the TRISCEND I registry population, one-year outcomes in over 100 patients, as a basis for our randomized trial. Today, we presented the phase I of the randomized trial. For those of you who might have seen, either been at the presentation or seen some of the slides, it's hard to understand, unless you hear an explanation, why we presented early results in a bigger trial. We received FDA breakthrough designation for the EVOQUE pivotal trial, and that allowed us a two-part trial design.
The original concept was that because this is a breakthrough therapy, there's no predicate. We had a lot of assumptions that were based on very little clinical experience or evidence. An early phase gave us a chance to pause, look at how the trial was going, and potentially make adjustments in the sample size, for example, or the duration of follow-up. The trial enrolled so quickly that by the time we got here to podium, the enrollment was finished for the whole pivotal trial. Our potential to use this early look to make any adjustments sort of evaporated in front of us in a very positive way. Nonetheless, we had taken the early look, and we wanted to share those results with our community.
And, for again, for those of you who were there, you see that we have, as we expect with the valve replacement technology, a near obliteration of tricuspid regurgitation, very different from tricuspid leaflet therapy, where some residual TR is typical. And for the pre-specified endpoints in this initial phase of the trial, limited number of patients, actually pretty remarkable quality of life improvement outcomes. So there's the background, and I think we open to questions now. Do you want to orchestrate the question?
Yeah, I think,
I don't know all the guys.
Marcus can do that.
Oh, okay, great. Yeah.
Marcus is JP Morgan. Congrats on the nice data today. I think a lot of people were struggling to put in context how do we think about what are the outcomes in tricuspid patients? What is the acceptable mortality, stroke, adverse event rate, serious adverse event rate, and how would you frame these in relation to other alternatives, or are there other alternatives for these patients? Thanks.
Susheel, do you want to address?
Sure. So, I mean, I think we're talking about a population that is fairly sick to start, that we don't have treatment options for. These are patients that are not surgical. So, you know, and so when you're talking about nonsurgical patients, you know, we looked at these patients were randomized to medical therapy, but we had a performance goal to look at the safety of the device. We had to derive that performance goal and those expected things from something, 'cause there was no predicate device. So we used a surgical series of 2,000 patients, and using that surgical series analysis, we had a performance goal of 43.8. If anything, that performance goal is probably underestimating what the mortality would be in the population we actually studied.
And so the event rates, the safety profile, you know, met the performance goal. The question you're asking, you know, what, what is acceptable? As a physician, not as anything else, lower is better. But, you know, the bleeding events were less than we saw before. They were ten, you know, 10%. Only 5% really were related to the procedure. You know, there were. And what the efficacy will be, you know, we see elimination of TR. Our hope and my expectation is that when we get the full data set at 400 patients, and we get the one-year mortality and heart failure, that elimination of TR will translate to a mortality and heart failure hospital benefit. That's hope, right?
That's what we're studying, and we just- we're not, we need to wait for the full data set for that.
Thanks. David Rescott with Baird. I wanted to follow up a little bit on the point you just made, but, you know, I think all week we've heard about how we can't make comparisons across, you know, two separate trials. But when you think about tricuspid and a repair trial and a replacement trial, those are theoretically two different technologies. So I'm just wondering if there's any implications we can read into versus both of those trials, especially when maybe you see in TRISCEND II, there is a better percentage of patients who have lower TR at six months versus those at one year with TRILUMINATE.
And then again, just, you know, what your view is on whether or not we can read into that as anything that suggests that mortality or longer-term benefits could be seen on, on the harder outcomes?
Let me start with that one
Yeah.
Susheel. First of all, it's really hard to make cross-trial comparisons, and the most obvious reason is that patient selection is very different. So we did not screen TRILUMINATE, TRISCEND II patients for TR acceptability or not. But the reality of how they were selected is that all the sites that were involved with the trial were involved with TEER tricuspid technologies as well. So broadly, these are patients that were felt to be either unlikely candidates for TEER or at best, probably suboptimal candidates for TEER. So trying to make a comparison between the TRISCEND patients and the TRILUMINATE patients on that basis is really difficult. And, you know, we talk about apples and oranges. This is a little bit more like apples and cows. They're really different.
Further difference, and you can see it in the way the case selection worked, the proportion of patients in TRILUMINATE who had New York Heart Association Class I or II at baseline, and their baseline KCCQ score are over 50, very different than a predominant New York Heart Association Class III and IV, and a baseline KCCQ well under 50 in the TRISCEND patients. So they are different patients, and that's really fundamental.
I mean, I can just add, at our site, we initially were in TRILUMINATE. Then we're in CLASP TR with the PASCAL device. At the same time, we were in EVOQUE. We screen patients for multiple trials, and Ted's point is right. How I approached it, you know, if you had really large gaps, 'cause it's anatomic restrictions with edge-to-edge, like, you know, TriClip or PASCAL, you need to bring the leaflets together. If the gap is too big, you can't bring them together. Really severe torrential TR, those patients we did—we put into TRISCEND. Patients with a pacemaker, and you see that in the trial here, nearly 40% had a preexisting lead. That's a challenge sometimes for edge-to-edge, and TRILUMINATE, I think it was around 13% or 15%.
I can't remember exact numbers. There are different populations. We used anatomic criteria. I do think from our, my experience in our site, these patients probably had more heart failure 'cause they had torrential TR. Because we didn't think we'd get a good result with edge-to-edge. If I thought I can get a good result with edge-to-edge and get mild, those patients went into those other trials, whereas torrential, I wasn't gonna reduce it to mild or moderate, and those patients I preferentially put into replacement. There is some bias in that regard.
Well, I'll make a quick comment. As Dr. Kodali talked about, there's such a huge heterogeneity in these patients that we believe the company having a portfolio of options, having more than one option to help treat the maximum number of patients, is the way we can treat the most patients possible, and that's really important to us.
Thanks, Chris Pasquale, Nephron. One question on the tricuspid side and one on mitral, if I could. The degree of TR resolution in these patients is profound in TRISCEND. At one point, there was some concern that taking a patient with torrential TR and resolving it could be detrimental to the right ventricle. Is that a concern at all?
Let's start there.
Yeah, absolutely. I mean, when you do a replacement, surgical transcatheter, you increase the load on the heart, and RV function can decrease. You know, I'll just go back to our TRISCEND I data, 'cause we don't have the echo and one-year data. We saw in TRISCEND I, as Ted said, it's in press and should be released today or tomorrow. When you look at one year, RV function does decrease. But RV function decreases, but if you look at... We looked at stroke volume, which is the amount of blood the heart is pumping per beat. Stroke volume actually went up. So yes, there is some the RV function will decrease, but forward stroke volume is what patients see in the cardiac output, and that improved. We do select some patients, right?
One of the exclusions for the TRISCEND trial criteria is severe right ventricular dysfunction. There are some RVs that are probably too sick to handle it. But we enrolled moderate, and we enrolled a lot of patients with not normal right hearts. This is something that we have to decide clinically. It's something that we're still learning. But we didn't see, you know, this is an area of concern, but we have to continue to monitor, but we didn't see, you know, from the TRISCEND I data, I think that's probably the most relevant sort of piece of information.
That's helpful. Thanks. And then for M3, this trial started well after the other two replacement studies that are being done. It seemed to enroll pretty quickly. Can you just talk about your experience with that product, how differentiated it is versus the other replacement products that are being studied?
I personally don't have experience with M3, Daveen.
I don't either.
I actually, before I joined Edwards, was an investigator in the M3 trial and had some experience with it with the first generation of the device. From a procedural perspective, it's very smart to create a wrap the cords and create a dock. That part of the procedure was the rate-limiting step with Gen one. They're now at least three generations into this docking mechanism, and I think it's quite slick right now. Once the dock's in place, putting a SAPIEN valve into that dock literally is a couple more minutes, 15, 15, 20-minute exercise from that point. Very straightforward. Several advantages. One is that it's a valve replacement product that's been used in tens of thousands of patients, so there's no uncertainty about the performance of the valve device.
But as importantly, many of the dedicated mitral replacement platforms have bulk, and they stick into the left ventricular outflow tract. Because the cords are gathered, the anterior mitral leaflet is pulled away from the LVOT, and left ventricular outflow obstruction is much less of an issue with the M3 platform. So I think it's very exciting that enrollment has completed, and it looks like this may be the first mitral replacement device to make it into clinical use.
Marie Thibault, BTIG. Just wanted to hear from the experts on the panel. Any thoughts on what we might hear at the advisory committee in January? Any thoughts on pushback? It's clearly great data, but will they be looking at, you know, patient selection, the short endpoints, that sort of thing? Just curious to hear.
Well, I'm not smart enough to answer that question. I honestly have no idea. I mean
Yeah, I think we can be confident that you have just started the list of things that will be asked about critically.
Yeah. Yeah.
Not intentionally.
But every FDA panel on every device ever have, has a critical examination of every aspect of the therapy. So I'm sure we're gonna be asked about patient selection, every detail of outcomes, including how TR grade reduction is assessed, and what's the meaning of patient-reported outcomes, such as KCCQ, and what other evidence might we have to support those outcomes? And because this is a first-in-class therapy, an assessment of what risk-benefit ratio is acceptable. So all of that.
Yeah.
We're very much looking forward to having that conversation with FDA.
Thanks. Joshua Jennings from TD Cowen. Just wanted to be clear on the January panel and then the approval timing for mid 2024. Should we be expecting the full 400 patient data set and one-year follow-up at the panel and driving approval? Or is it possible that the 150 patient set is what's gonna be put in front of the panel and submitted?
I'll say, just a reminder, we announced in our Q1 earnings that we finished enrollment at the start of our Q2. So no, the 400 patients with one year is not available for a January panel date.
Thank you.
But we expect the totality of the data we have available to be at that panel.
Excellent. And then, Daveen, just a question for you on the CLASP IID 12-month data. Has there been a hang-up in the clinical interventional cardiology community about just having 6 months for backing PASCAL, or is this kind of a clearing event? I don't suspect it's a big one, but maybe just a little one. And then also, just, can you just remind us of the premium pricing strategy for PASCAL, and whether that's still in play? Thanks a lot.
Maybe on the first question, I'll have Firas kind of answer, answer the first question and talk about, hey, 12 or 6 versus 12 months data. What, what have you guys thought of the physicians and to the physician community?
Can I comment on one thing? I mean, by no means, I have no idea what's gonna happen with the FDA, but I'm trying to predict what's gonna happen between now and the FDA. I think what we've all seen in our clinic, the flood of patients on tricuspid regurgitation that are coming for therapy. You know, quite honestly, the way that we have enrolled patients in this trial, patients are willing to jump through all the hoops to get into therapy, and then if they don't get in one, they're so desperate to be treated, they jump through the hoops again to get into, you know, the other therapy. I anticipate that our clinics, between now and then, are gonna get busier with patients with TR that are looking for therapy.
You know, to your questions about, you know, the one-year data, I think it is, one, it confirmed what was presented last year with the full cohort. And two, it, it helped us gain a lot of confidence in the sustainability of the therapy. I think a lot of us worry that TR, the disease, might come back, and the results that were presented today were very reassuring that the results that we've seen early are sustainable to, you know, one year. And, you know, quite honestly, with the majority of them having, no more than mild mitral regurgitation, which is, you know, very encouraging if you're counseling patients about how, to best treat, their mitral regurgitation. Now for the pricing, I give it back to the-
Well, before you answer the pricing, Ted, you want to talk about the totality of the data that we're seeing beyond just 2D?
Yeah. Thank you. We do have an early feasibility study, and we've reported and published at least 3-year outcomes and shown some small number of patients with 4-year outcomes. In terms of the way the community accepts the results from this therapy, this, TR as a class, is an established therapy, and I think we've understood for a long time that early successful outcomes with this therapy are generally durable. If we see a patient who reaches 30 days with a stable outcome, their 1, 2, 3, out to 5-year outcomes are pretty predictable.
We did put a little bit of nuance into this with our registry, demonstrating that the more complex the anatomy is, however good the results are, they're a little less good than in the simpler anatomy, which is not a surprise, but I think we've quantified that to some degree with the registry.
So to answer your last question, if you look at PASCAL overall, the PASCAL program in its entirety is not only a collection of clinical data, the different types we've talked about, it's a collection of innovation, many generations of products. We've already on our second generation. We brought in Ace, and we're bringing out new technologies literally every, almost every year for the next couple of years. And then it's a comprehensive high touch model, where we love to work very closely with physicians to help with the pre-case plan, to ensure that during the case we get the optimal results. So PASCAL, to us, is an overall program, and we believe that program and the results we see from the product are differentiated.
As a result, we do have a small price premium above our competitors, and we believe that's warranted by the differentiation we and we believe our physicians see from the PASCAL program, including the data.
So much. Matt Miksic from Barclays. So, it was one, you know, kind of a two-part question around the reduction of TR and the potential, you know, correlation to mortality, you know, that came out of the TRILUMINATE data earlier in the year. That without a mortality benefit, there was a lot, you know, quite a bit of debate as to whether we would see that and if not, whether it was important, the device without it, just to make patients feel better. And so first question is where do you come down on that? I'd love to get your thoughts on, you know, the belief that unlike MR, that we may get further down the road and see that there's just really not a super clear mortality signal from lower TR.
And then I just one follow-up.
Maybe I can say a couple comments. Let's take the therapy out of it. We, we had- we've had now to the date, I mean, for a long time, they ignored tricuspid disease. In the last decade, we've had multiple, a multitude of sort of papers. And, and you, and when you adjust for other sort of confounders, more TR leads to worse outcomes. Take therapy aside, patients with torrential TR had higher mortality than patients with severe TR. And you account- and that analysis is accounting for other confounders, you know, poor heart function, pulmonary hypertension. T-TR is bad. In terms of the question you're asking about is quality of life, how important is it? Well, from a patient perspective, most of the patients that we're, they're averaging 78, right? They're not looking for 20 years.
Heart failure, whether it's left-sided or right-sided, is a miserable way to go. It's a miserable disease. You're fatigued, you don't eat, you... And so the patients are coming because they wanna feel better. They're not coming to say, "I, I, I need you to make me live longer," because at that moment, that's not what they're thinking. They want, first off, I will say from a patient perspective, it is probably the most important thing. The KCCQ, which is well-validated, and this meeting is actually good because we got some presentations validating it in TR. The improvement of 21 points, you know, minimally relevant improvement is 5 points. You know, and then when you get to 20, it's a large improvement. It's comparable to what we saw in some of the TAVR study. It's a large improvement.
And then I take that in the context of everything else. If you have a large KCCQ, if other things, your echo parameters, your RV function, your stroke volumes are increasing, if we see trends, potentially in heart failure and mortality, those are all would be encouraging. I don't... You know, I think one of the things that I personally, and I'll just say this is, I think, the TR trials, I think if we followed these patients longer, the difference in mortality may take some time. I mean, in some ways, like COAPT, right? It was two-year. But I think you are gonna have to look at the totality of everything. I think we look at all the markers, but I, you know, quality of life is important, and that's what the patients are looking at.
But I think alone, sure, maybe not. But that magnitude with other parameters and everything going in the right direction, and I think if we had a large, longer follow-up, 'cause we've seen from every study, TR is bad.
Yeah.
So there are two presentations today that I think are important in this discussion. One is Suzanne Arnold from Kansas City, reported on the correlation between changes in KCCQ and mortality and heart failure hospitalizations in TRILUMINATE, where those clinical endpoints by themselves didn't reach a level of statistical differentiation. And she showed that with larger KCCQ improvements, mortality appeared to be better, and heart failure hospitalizations appeared to be better. So one of the challenges we have, we heard the term heterogeneous used to describe this population, is figuring out in which part of the population can we get these more predictable, and you know, we all like harder endpoints.
We also, and to the whole business of patient preference, we reported in a moderated abstract today, with Colin Barker from Vanderbilt, as the first author, a study on a patient preference survey in this tricuspid population. And, there are about a dozen variables that they ranked in order of importance for them. That is, if they're gonna be treated, what's important to them to get out of it? And, improvement in the ability to have regular activities of daily living and improvement in shortness of breath were the top two. I don't remember exactly what was number three. Living longer was not rated as a priority. It is all for the patient, all about the quality of life.
That's helpful. You almost kind of answered the second part of the question, which was, you know, just if we- you mentioned earlier, Dr. Kodali, that you hope, you know, that this sustained reduction is gonna show the mortality benefit. But if we get to that point- you know, does this become, you know, obviously, you want the mortality benefit. Does it become a disappointment, and we kind of pack up and move on? Or does it become a discussion about all the other benefits of, to these patients, and then, and then a, you know, discussion of the way forward in terms of approval and coverage and all the other things we'd expect?
Yeah, no. I mean, I definitely don't think we'd pack up and move on. As I said, I think it's really about, for me, I think these quality of life outcomes are important. I know it is not satisfying to have, like, a hard endpoint, but I think if the trends are in the right direction, it's reassuring. Now, if the trends are not or they're opposite, which I don't, you know, I have no reason to, but yeah, sure, we'll have to reassess and say, well, how does this mean? Is there a Ted's point, is there a population that we need to select out, that we treat better?
There's a lot of what-ifs, but I really feel strongly that, you know, it is wrong to dismiss the quality of life as an important outcome. We do a lot of things, you know, to make patients feel better. And this, when we see patients in the office, that's all they're caring about, right? It's a miserable existence. And so as physicians, I may not see them in two, three years, but I'll see them in a month, and if they're feeling better in a month, they're really happy.
There's another comparator that it's not a fair comparison, and it puts a perspective on it. I've never heard anybody complain about hip replacement not providing a mortality benefit. You know, there's a totally 100% quality of life intervention that we, as a society have recognized, is important because it's all about quality of life. It's interesting to me that we have become overly focused on mortality and heart failure hospitalizations in our cardiovascular trials.
Right. I think it's true. I think we can't create harm, right? And that's what we're looking at. But I personally believe that if we go long enough, this leads to better survival. I mean, that's all these trials show TR is bad, right? So I gotta assume, but I guess that's a dangerous thing.
Joanne Wuensch from Citi. The data sets were great. Thank you for that. I'm still curious about the uptake. I think some may think that the mitral market has not grown at the rate that was expected. I'm sort of curious, how do these clinical data translate to patient usage and uptake? A part of that is my question on, in tricuspid. Do you have wait lists for patients? How are they currently being treated today? Are we reaching a tipping point, any of us?
Yeah, I mean, thank you. That's, you know, that's very relevant question. And, you know, to be honest with you, you're right. I mean, if you look at the growth in mitral procedure, compare, for example, with TAVR, it is not parallel. And part of it is, you know, for the longest time, we had only, you know, one therapy, and we trying to, you know, fit everybody with one therapy. And I think right now we have more data coming out. We have more therapy that is available for the patients.
We, for the first time, start seeing data saying that even in those not so favorable anatomy, that you can treat them with TEER, and you can achieve, you know, good outcome for those patients with very low mortality and significant improvement in quality of life, as we've been discussing for the last, you know, few moments. So I'm hoping that this will increase the confidence. It definitely increased my confidence as a treating physician, that we can treat those difficult anatomy, where in the past we were shying away from them or not confident in treating them, that we will be able to treat them and, you know, and get a good results and very, very low adverse events at one year.
So it's safe and effective in a broader patient population with the data that was presented today for both the randomized and the registry confirming that. You know, to your questions about, you know, tricuspid, I will tell you in our clinic, and I live in an average, mid-sized city, the clinics are. Our clinic right now is, you know, tricuspid is, we are thinking about opening a separate clinic for, you know, for those patients because there are so many of them. And as more data coming, more patients are coming and asking for it. So I, you know, I anticipate that after the data today, that will continue to grow as well, and I think we need to start thinking about care pathways for those patients so we can treat them promptly.
I might just add one thing. Your comparison of mitral to tricuspid is important, but there are significant differences. On the mitral, especially when we're talking about functional or mixed disease, the heart failure community, there's also a lot of other therapies for mitral disease, for medical therapy and other options that sort of delay the progression, and then also, a lot of those medical therapies improve outcomes. There's a long path of patients getting to- before they get to us, and there's a lot of bias. Our heart physicians, we're aggressive LVAD transplant center, and they really are aggressive on that. Our heart failure physicians on the tricuspid side don't have other options.
I get much more referrals from heart failure for tricuspid disease than mitral disease because they're stuck. They don't, you know, they've treated their left side disease, and they're not, they don't have any other levers to pull, and they're more likely to send us a tricuspid patient. So I think the two, I personally think the two path are different, and the uptake will be different. I don't know if others want to comment.
Well, maybe you could each comment on the difference in how many referrals you get for mitral versus tricuspid from your surgical colleagues.
Right. Very little on the mitral side, almost zero, 'cause they like to operate on mitral patients. And they send... No one really wants to operate on a tricuspid, and then oftentimes, sometimes the patient's not a candidate anatomically, and we have to send them back, and they're like, "Well, look at another option." And there's a lot of that from the surgical side.
Yeah, I mean, I think one thing for sure, that the awareness of mitral disease and tricuspid diseases has increased significantly in the last year, and it will probably increase even more in the upcoming year. I think the tools that are available and the confidence that is increasing with the available therapy, it is going to increase the confidence of the treating physicians to refer those patients to a center, so they can get treated.
Well, I'll just make a comment on the market overall, right? To be fair, from our side, you know, we obviously just had our results yesterday, but we continue to be very pleased by actually the overall market growth, right? We see overall TMTT market growth in both the U.S. and Europe well into the double digits, so we feel very confident in that. We see, particularly in Europe, that relatively, tricuspid is probably growing at a higher rate than mitral. And so for us, we think that the uptake of these, the growth of these markets is happening. There are more patients being treated. There are more people coming to cycle in through the system. In Europe, where we do have a tricuspid treatment available, we continue to see even stronger growth. So we're definitely pleased by the overall market growth that we see.
Dr. Kodali, so I think another mitral comparison. So we see, you know, better efficacy with replacement here. Looks like more, more adverse events compared to repair. In mitral, we see, you know, TEER has done well relative to replacement. Why is this market not going to evolve the same way? Who's going to get replacement? Who's going to get TEER in, in tricuspid? And secondly, the anticoagulation question, how long are these patients going to have to be on it? How do you know if they should be on a DOAC or warfarin? Thanks.
So in terms of the first question of, you know, TEER and replacement, you know, I think that's gonna evolve over time. There are different factors. I mean, as we said earlier, there's a lot of anatomic factors that are gonna dictate one therapy over another. There's also, you know, what your expectations are. If I can get it to mild, my thought process is different. If it's torrential and I'm not gonna get it significant, I'm not gonna expect a clinical improvement. The TRILUMINATE data also shows if you don't get a good result, the magnitude of improvement in KCCQ and the clinical event rates are higher. So in that patient, yes, the risk profiles of the different therapies. TEER risk profile is different than replacement.
You know, pacemakers being the main one and some bleeding issues. But if I want to really treat the patient, I'm gonna go with replacement because it's a risk-benefit analysis. But if I feel very confident, obviously, that it would be mild, then it's one thing. So that's one clinical point that's gonna make a decision, because there's a lot of these patients that we see that I don't think I can get a good result with edge-to-edge. I'm not gonna get the clinical improvement that I need, so I'm gonna favor a replacement. The other thing that's important and interesting, we talked often about the learning curve of a procedure. The learning curve of a procedure is not just for interventionalists like Firas and myself, it's for the imager.
TEER, it can be challenging, and people are getting more experienced, but TEER has more limitations and more imaging challenges to be able to image the leaflets. One of the things with replacement, those same imaging. Yes, you have to image, but the degree of what you need to see and what you need to see is different. And that's borne out in this trial when you look at the procedure times. You know, the mean device time was 65 minutes with not that big a confidence interval. These were initial trials, right? And a lot of these centers hadn't done. So it was a trainable procedure that was reproducible with support from excellent clinical support from the Edwards team, and, you know, that really dictated it. But with preoperative screening, it was a more sort of procedure.
For a lot of physicians, where those imaging challenges, my- I have an excellent imager. I think I have.. I won't comment on Scott's, on Firas's, but I think ours is the best, right? And see, Becky Hahn is all over the place. She sees things really well. Someone down the street may say: You know what? I'm not confident I'm gonna get good images. Where I might put a patient in edge-to-edge because she's confident, there's gonna be a low threshold to say: You know what? I'm not sure I can see that well enough. I'm, I'm... Replacement has that, that little, that bar that's a little bit easier to, to go over. There's a lot of things that are gonna play a role in how people decide. Risk profiles are different.
Efficacy in terms of TR reduction is different, but there's also procedural characteristics, not only in the anatomy, but how the team and their learning curve and what their level of confidence that are gonna dictate some of these things as well. Oh, anticoagulation, yeah. I think the reality is, right now, I anticoagulate these patients lifelong, whether there's gonna be options and whether we can understand. But the reality is. 97% is based, I think all but one or two were in AFib at baseline. The vast majority are on anticoagulation at baseline. So, you know, it didn't really change. In the trial, we didn't mandate warfarin or DOAC. You know, it was sort of patient-physician preference. If they're on warfarin, I generally continued it.
If they're on DOAC, I generally continued it, so it was sort of my attitude.
One of the reasons the protocol doesn't specify exactly how to manage the anticoagulation comes back to the heterogeneity of the population.
Yes.
So, these are patients who have a history, frequently, of, other chronic illnesses, including, bleeding episodes. So the choices to anticoagulate with warfarin, versus a DOAC may depend a lot on whether the patient has a history of bleeding, whether they have permanent, atrial fib or not, antiplatelets, for whether or not they have coronary disease or stents, or other vascular problems. So it's really a broad spectrum of patients. At this stage, we don't have enough experience to really lay out a decision tree for anticoagulation therapy.
Time for one more question, then I'll ask Bernard to come up and close us out. Who wants to... Anything else, Chris?
So you talked about new pacemaker implants being one of the main complications we see. It's somewhat of a unique challenge. We're already treating the tricuspid valve. Any special considerations about being able to effectively pace these patients, whether that could compromise the effectiveness of the valve you just put in?
Yeah, no, great, great point. So, and that's an important consideration, and for these tricuspid trials, you know, we talk, always talk about the heart team. In tricuspid disease, the heart team gets bigger. Not only do we add the heart failure specialist, but we also add an electrophysiologist. And so before we go into a procedure, we have a pacing plan if there's any conduction issues. And so, because you raised the point, you don't want to put a lead across your fresh valve, because that may impact the valve durability. In TRISCEND II, there were 14 new pacemakers, and it was about a 50/50 split between patients. But we just avoided putting a lead across the valve.
About half got a coronary sinus lead, and half got a leadless pacer with Micra, and there was one patient that got a epicardial lead. The reality is, the whoever the EP is, there are EP docs that are really familiar and really fast with Micra and leadless, and they want to do that. There are EP docs that do coronary sinus all the time. We sort of have a plan with our docs. Our institution, the EPs preferred the coronary sinus lead, so that's what we did. But we try to avoid it, going across the lead for the reasons that you stated.
Well, that's a great discussion and a great place to stop. Bernard, if you would do the honor of closing us out. Thank you, Ted.
Yeah, no, so thank you so much, you know, for spending, you know, so much time with us here this week. I know it was, you know, not typical. You know, as a team, we thought about it, and we said: Are we going to have, you know, three investor event, you know, this week? And we did it. So we really appreciate the fact that you came to all of the events until, you know, late, you know, Thursday. What I want to do now is offering some closing thoughts. I'm going to be short. I'm conscious of time here for all of you. So why on TAVR?
You know, after 20 years of us, you know, bringing, you know, a ton of science, evidence, more than 1 million patients, 8 New England Journal of Medicine, and this year, PARTNER 3, you know, 5-year results. In addition, I think it is an important point, you know, the many patients underdiagnosed, undertreated around the world, we believe that TAVR is very well positioned. Our TAVR platform franchise is very well positioned for short-term, mid-term, and long-term growth. You know, in addition, you know, our two strong businesses, core businesses, surgical and critical care, are doing extremely well. They are getting big, we have a pipeline of innovation, and we know that they are going to produce, you know, durable growth. In TMTT, you know, we moved from adding a vision to now, you know, adding a portfolio.
We have achieved, you know, many milestones, like you have seen here this week. And we believe, you know, TMTT is becoming, it is not just will become, but is becoming an important growth engine for the company. It will help, you know, many patients, and, you know, will continue, you know, to be a growth engine, you know, for the company. So altogether, we see a tremendous opportunity. We are going to remain focused, you know, the only company at being a pure play. You know, we believe about, you know, this patient focus, bringing breakthrough technologies and our leadership, you know, to be, you know, this kind of leaders where we are going to deliver sustainable growth, again, short, mid-term, and long term.
Thank you so much, you know, for being, having been with us, you know, all week, and I, I look- very much looking forward to see you in December. Thank you.