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ACC 2019 Wrap-Up with Dr. Valentin Fuster
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ACC 2019 Wrap-Up with Dr. Valentin Fuster
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Language: EN.
Segment:0 .
Good morning to everybody. I am Valentin Fuster and it's a pleasure to discuss this morning what went on in the American College of Cardiology meeting in New Orleans. I do this as the lead director of Hurst's the Heart. It certainly is a pleasure to visit every national meeting to discuss with all of you aspects that may change the way we practice.
This meeting, overall, was interesting. It was a high density of studies that each of them, I think, add the niche into our practice, and I will be discussing 11 of them. Nine of them were breaking trials. Two of them are interesting, and therefore I thought that it was worth it to present. These are the topics we are going to be discussing. First, TAVR in low risk aortic stenosis patients, there are two studies that address that aspect.
The second is the Apple heart study, you know, watching your watch and see whether you're developing atrial fibrillation or not is interesting. The other is the use of apixaban, the AUGUSTUS study is the use of apixaban together with a platelet inhibitor in patients with atrial fibrillation and stenting. Then, there are a number of pharmacological studies, the bempedoic acid, which is the so-called CLEAR Wisdom Trial, is basically, it blocks enzymes that participate in the synthesis of cholesterol like statins do and work more proximately; it was interesting information.
Then we have the new agents that are now addressing diabetes in a way that is quite hopeful. Dapagliflozin in heart failure. As you know, the previous studies with these new groups of agents show that glucose in patients with diabetes is not absorbed and you can decrease the glucose levels in blood, but it was quite interesting the curiosity in which hospitalization for heart failure in all these studies was significantly decreased.
And the question is, what is the role of these agents in diabetic patients who actually have heart failure? A very fascinating type of an approach. Then, you know in all the devices we use, one of the problems are infection. And can we use the device with an envelope that contains an antibiotic that is slowly is released and prevents such infections? This is another study that we-- the WRAP-IT study.
Then the question, a patient has a cardiac arrest and certainly, I think you agree, in a patient who has a cardiac arrest, the first thing we do, aside of the resuscitation, of course, is to do a coronary angiogram. But the question is, should all patients who have a cardiac arrest undergo angiography? I think this is an important question. And then we have a fascinating, at least something to think about, it is challenge that dual antiplatelet therapy should be given more than a month.
And maybe we should give one agent after one month and is enough. This is a challenging concept that was brought up in this particular meeting. Then we have two studies which are not breaking trials, but one is the primary prevention guidelines, and the other is that, can we make ticagrelor to be reversible? That is, do we have any agent that can block ticagrelor on patients that we are concerned because of bleeding and to act rapidly?
These last two studies were not part of the breaking trials. So, a lot of things to discuss and I will say, to start, the sense of this meeting is that each of the studies that we're going to be presenting have a positive note that we are advancing inch after inch, and I think this is the good thing about the meeting that we attended. Each of the studies, as you will see, make something new that has practical implications.
Now, let's begin with the first one.
Segment:1 Discussion of PARTNER 3 Trial.
It's easy to say there were two studies in TAVR in low risk patients, we should discuss both together. Actually I'm not going to do that. One after the other because they're different. And interpretation of the data is different if you look very carefully the way the studies were actually portrayed. So let me begin with the first one, which is the PARTNER 3 investigators study.
Michael Mackk from Texas presented this study. Well I think you all know that in patients with aortic valvular stenosis, who actually are at the high risk, very high risk or intermediate risk, different studies have shown that TAVR is equally effective or perhaps even more effective than SAVR, than surgical intervention.
So this field has evolved over the last eight, nine years very rapidly to the point that now we have two trials, and this is the first one in which patients at a low risk address the question. And actually the STS risk was an average of 1.9%. So it's very low. So patients with aortic valvular stenosis that otherwise are healthy, other than the aortic valve, this is the group that we are going to be presenting.
Well the first one, as I mentioned, the PARTNER-3 study, the patients were randomized, I think there were actually 1,000 patients in 71 centers. And 1,000 patients with this low scoring of risk were randomized into TAVR versus surgical intervention. It is important the primary end point because it's different in the second study we are going to be discussing. The primary end point here was death, a stroke, or rehospitalization at one year.
I emphasize this because in the second study, rehospitalization was not part of the primary end point. The primary end point in the second study was just death and stroke, and it's very important in the interpretation. And here they look at two possibilities, statistically is a noninferior or superior, the TAVR in the context of SAVR. So, I will go directly into the results by saying that at the primary composite end point, and I mentioned the three stroke, the hospitalization and death was actually 50% reduction in the TAVR versus the SAVR.
It went from 15% in one group, the surgical group, versus 8% in the TAVR group. And this is the data at one year of follow-up. Very fascinating. But there are other things that were positive. And that is the combination of death or stroke together, and then there was decreased incidence of new onset of atrial fibrillation. It was significant in the TAVR group versus the SAVR.
And then certainly there was a shorter hospitalization rate which was part of the primary end point. So, this is exciting but I want to make a comment that is important. People begin to believe that now we are getting into younger and younger people, which are those at lower risk. And the question, of course, is what is going to happen with this bioprosthetic materials when you follow these patients for a number of years?
Here's the main point. We are going to younger and younger but not so much. In fact, the original studies in the PARTNER, the average age was 80 years. In here we're talking about 75 years. Because the younger people do not have this kind of aortic valve stenosis, they have bicuspid aortic valve, and these patients were completely excluded. So let's be sure that we do not confuse low risk with much younger population because the much younger population with bicuspid valve were excluded from these particular studies.
So I think the news are quite fascinating, are great, and just FDA approve the intermediate risk just a week ago. Now I, probably, again, I'm sure they will also prove this one in the next few weeks. So, there's a change now in the way of thinking. We used to think the patient with aortic valve stenosis needs surgery.
But perhaps we might consider TAVR. The thinking is changing. The patient with aortic valve stenosis and excluding bicuspid valves, aortic incompetence, large aortas, is going to have TAVR. But maybe is not feasible for TAVR and we do aortic valve replacement, a complete change in the field. It took place just in a few years. It's a fascinating story.
Segment:2 Discussion of Evolut Low Risk Trial.
Now I'd like to move into the second paper which is the same, transcatheter aortic valve replacement. First of all, in the first one was the balloon expandable valve. Here is the self expanding valve, the Evolut approach. Now this paper was presented by Jeffrey Popma. It has very similar entry criteria than the previous one, the thoracic surgery score is about 1.5, so these are very low risk people.
And the number of patients entered here was actually 1,500. In the first study were a thousand. But there are problems in this one, in which they only go into one year of follow-up with 850 patients. So they didn't go into all the group, just this part of the whole group. They wanted to put this paper together with the other one, I believe, that's probably what happened. Well, so out of 1,500 patients, 850 were randomized, as I mentioned, TAVR with the self-expanding approach versus SAVR.
The end point was only death or a stroke. This is critical. There was not hospitalization. I'm saying this because when one reads the second paper, will say this is not so good as the first. And it's as good as the first, maybe even better, but the fact of the matter is, the primary end point which really play a huge role, the hospitalization. On the first one here, hospitalization is not the case, I think it's very important interpretation of the data.
Actually the bleeding complications were less in TAVR, the same renal injury, atrial fibrillation like the other. But there are two issues that I'd like to discuss. The first one, is when you look at both studies, this particular one, actually the results are more striking. But the incidence rate of events is much lower. And I could give you a sense of what I'm talking about.
First of all, if you really would look at death in a stroke, in this particular study the results were better. If you used this primary end point, we compare with the other one if you exclude hospitalization. So it's very important, hospitalization. It makes that 50% reduction, but not the stroke and so forth. The same happens actually with mortality. It's fascinating. In the other study, the first one, mortality actually went from 0.5% to-- in this one, in the second study I'm presenting, is 0.5%, 1.3%. In the other, the mortality was significantly higher.
So, still in favor of TAVR, but the results are more striking in this one, so I think that, and the same happens with even hospitalization. Once they look at hospitalization, in this second study, the results are more striking in favor of TAVR than in surgical. So I think it's very important that we don't get caught into the problem that this study is not as good as the first. It's equally good, or even better. But, here comes my second comment.
A problem with heart block and with aortic regurgitation. And this is an issue of the second study. In fact, the incidence rate of these two issues at 12 months was aortic regurgitation 3.5%, significant aortic regurgitation in the TAVR group, versus 0.5% in the SAVR group.
In pacemakers, 17% in the TAVR group versus 6% in the SAVR group. This type of data is certainly significantly worse than in the first PARTNER study, in which the approach was with the balloon expanding. And here's the self-expanding. And you say, what is the future? Well, this is the story. The Evolut new valve, that really significantly decreased aortic regurgitation in pacemaker need was only used in 21% of patients.
So the remaining patients, they still use the old type of prosthesis. So I think that the results are not good in terms of pacemaker in aortic regurgitation, but when we have to really now pay attention with the new Evolut valve, in which such a problem is much less. But we cannot make a comment based on this study. So I would like to summarize by saying what they said that they say, really, patients with aortic stenosis today, excluding bicuspid valve, excluding very large aortas, aortic regurgitation, such patients should undergo TAVR.
And maybe some, we may look, if it's not possible, to ask for surgery, completely. A complete change in the way we see the situation we used to talk about. Well, this being said, let me now move into the Apple heart study.
Segment:3 Discussion of Apple Heart Study.
This brought a lot of attention. In fact it was the first breaking trial being presented because it was thought by the organizers of the meeting that this was the most important study.
I'm sorry I have to disagree. The two most important studies were already presented here. I think this study is something that is exciting, is interesting, and actually, I think it opens the door of an aspect that really we are all worried about it. I would say that more than 50% of patients who have atrial fibrillation, they don't know they have it. So let's start here. And it's not unusual that the first manifestation is a patient who has thromboembolic or cerebral emboli, and then we start thinking we go to the venous type where there is a patent foramen ovale but many of these patients, probably two-thirds, is actually emboli from atrial fibrillation that is identified afterwards.
So it's an issue. Can we identify these patients before? This is the question that has been in the minds of everybody working in the field for a long time. And certainly this study, in my view, is a positive approach, a first approach to this. The study was presented by the group at the University of Stanford, Mintu Turakhia and Marco Perez from there, and what is interesting is how they were able to enter 400,000 people in less than a year.
Don't ask me to answer this, but it seems people like these devices, otherwise, it's impossible to, I have never seen a study of such magnitude with an entry of so many people in a short period of time. And if I made the comment of patient, it's a mistake, these are healthy people, all of them, and this is actually across the country. And what they did is, by plethysmography, you have the watch, and when there are irregularities, this goes to a central station.
And that central station looks at the irregularity, once, twice, three and once you see several, they send a message to the patient wearing it-- I'm sorry, to the healthy individual wearing this watch and say, "You may be in trouble." Then, what happens? Two things happen. One is, there is a system that somebody local is contacted and they go and they do the appropriate things Holter monitoring on an electrocardiogram and so forth.
And the other is, they mail to you a patch and then you transmit centrally within the first week, the first 90 days. So you can go very quickly to see what is going on or you may be a little bit delayed. Well, the results of this is that, if you go quickly, near 80% of people that were identified by recurrent irregularities, in fact they had atrial fibrillation. If you wait just until the patch comes in, it's 31% of people.
So it's surprising that whatever the screening is on the central station, it's really worth, and there are no details because there's no paper. We are dealing with an abstract and with few slides that were provided to us but very difficult to know the details or what really goes on, how the people centrally screen these patients, we don't have any idea. But it certainly works, and this is the reality.
Now there are several things that I think are worth mentioning. First of all, the number of people who had atrial fibrillation was 0.5%, which is much lower than what you would expect in a population. But why? Because the average age was 40 years. So basically, these were healthy people with a large number having 25, 30 years, these are the people who are all constantly looking at their watch. And they didn't enter a large number of people who we call high-risk, that are people over the age of 75 or so forth.
So that's why the incidence rate was 0.5%. But at least the method actually worked, and the question is, where this is actually going. I think this is the first step in an important aspect in health, and that is, can we identify people with atrial fibrillation? But, having an interest in primary prevention, one thing I learned over the last few years is that the primary prevention, everybody talks about, but the adherence to the primary prevention tools is very poor.
And I don't have to go into the details to give you information about this. Now interestingly, of these 400,000 people, those who received an alarm, only 50% reacted to the alarm. So it's already telling you that, it's very nice to talk about it, but the data presented to you is the data of those who reacted. I didn't present to you any data, and I don't have any information of the 50% who didn't care whether their alarm came or didn't. So I think, as I look at the future, to say the whole world is going to wear a phone or a device, this is very difficult to say.
Two-thirds of the world are middle or low income, and I cannot see cost effectiveness if we are going to move into this direction. So I want to give a lot of caution to all of these. I think it's exciting. I think they're addressing an important issue, but the practicality of this, of how this is going to work in the future, to me will be a few people who are very obsessive about these kind of devices, and I am not at all-- most important people are high risk.
I can see people who are hypertensive and they have few APCs or people who are diabetic or people who, you know, alcohol and so forth, that you may identify a group in which this will be actually even mandatory, in terms of the prevention of thromboembolism. So this is what I can say about the Apple heart study.
Segment:4 Discussion of AUGUSTUS Trial.
Then, we move into something which is very interesting to comment on.
The studies of interest, and this is, you have patients here with acute coronary syndromes, so you are dealing with stenting in most of them and if not, it's still, you have to do dual antiplatelet therapy. And these patients have atrial fibrillation. This is actually the type of patients that I'm going to be talking about, the so called AUGUSTUS study. This was presented by the group at Duke, the Duke Clinical Research Institute; Dr. Renato Lopes presented this study.
And this is the question. And the question is, what do you give to these patients? Do you give triple therapy or you give double therapy? And if you give double therapy, what therapy is double therapy? Well, let me stop for a moment and go backwards a little bit and what is in the literature today. And the literature today is that dual therapy with rivaroxaban and one of these PGY inhibitors, or dabigatran have shown in dual therapy to be better than any anticoagulant, conventional anticoagulant or triple therapy in terms of bleeding.
The whole issue's bleeding as you can imagine here. And if you prevent bleeding by a simple approach, are you in a way giving more ischemic events? But the issue is bleeding. Well the dabigatran data and the rivaroxaban data already suggested that given in a dual approach with a PGY of these drug inhibitors, actually, the bleeding incidence is less than if you give conventional anticoagulants in a dual way or triple therapy in any way.
So, this is in the literature. Now we have apixaban. That's basically the third one that comes into it. The study is actually very complex, but it's elegant because it's how they can do a study like this, and I will tell you basically the concept. The concept was to use apixaban. Most of the patients were 5 mg twice daily. Some of them was 2.5 mg twice daily.
Those were people over age of 80, people very thin, less than 60 kg and creatinine levels more than 1.5. They give apixaban versus conventional oral anticoagulants, warfarin. And these two groups were associated actually with a P2Y12 inhibitor. In fact, this was clopidogrel in most of them, and in some of them was ticagrelor.
But, each of these two groups, they had two arms each group. One was added aspirin, triple therapy. And the other, no aspirin. So you basically end up with six groups of people. Very well done, this study. And the results, I can tell you, are fascinating in this sense. Number 1, the great winner is just the apixaban with clopidogrel. In terms of bleeding, significantly less than in any other group. Okay? That's number one.
And then the groups that did the worse is when aspirin was added. In particular, when aspirin was added to the warfarin and the platelet inhibitor. And all the others were in between. I don't have to go into the details. So basically, what we found here in this study, at least what they said, is that dual therapy with apixaban and in this case, most of them was clopidogrel, is the way to handle these patients. Here it brings an issue that I think is important to discuss, and it's the issue of guidelines.
So, when you go to guidelines, 2017, this is about one and half years ago, looking at the American guidelines and the European guides, it still is a mess. And even if you look at the key table in the European guidelines, you have to have a very high I.Q. to really understand it. With a triple, double, and all of these, it's very messy. And the question is, how responsible are the guidelines of one and a half years?
Now we have dabigatran dual therapy, we have rivaroxaban double therapy, we have apixaban, and we still will talk about the guidelines of 2017. Which brings the issue, there is an important meeting on March the 28th to discuss guidelines in general by the American groups, the AHA and ACC, and that is what guidelines mean and where we are going. And I think the sense that one is beginning to really think naturally, Dr. Jonathan Halperin was the head of the guidelines until very recently, and I think he will agree too, I think we have to do updates and just work with the updates, and leave the main guidelines for the lawyers.
I did a survey on the editorial meeting for JACC in the American College, and there were a hundred people there. They were all participating as editors in JACC. The first question was How many of you read the cholesterol guidelines that just came out? And then you got one out of hundred. Second question How many of you read the guidelines of hypertension that came a year ago?
Three out of hundred. So we have a problem. And that is, we have huge documents. And I will talk in a minute about the primary guidelines that just came out in this meeting. We were given, thank God, only the executive part, the executive part is like this. So I assume the other is like this. So, the question is, this study, to me, the apixaban study, is a clear example that we already know for more than a year that we should use two agents, but still we keep quoting the guidelines of a year and a half and using three, use two, three, and so forth.
In this study, by the way, the ischemic events did not increase by giving double therapy, which is apixaban with clopidogrel. So basically, it's an interesting study and again, I think we are moving into this particular mode. Later on we can have some discussion.
Segment:5 Discussion of CLEAR Wisdom Trial.
Here we come into the next study in which the so-called bempedoic acid approach.
This is the so-called CLEAR Wisdom Trial. Let me tell you first what I don't understand. What I don't understand is that the New England Journal of Medicine comes with a similar study published three days ago and it's called the CLEAR Harmony Trial, and what was presented in this meeting by completely different people, no connection, is the so called CLEAR Wisdom Trial. How the New England Journal comes with the other group and doesn't present this one.
Don't ask me why, but everywhere was a question mark in the whole place. Nobody really understood. Having said this, the one published in the New England Journal of Medicine involves near 3,000 patients and the one that I'm going to be presenting here is about, I think, 750. The results are exactly the same. So let me start by saying, there's no discrepancy. But I have to focus into what was presented in this study.
And this was presented by the group at the Ann Arbor, Michigan and Goldberg presented this study. And certainly he make a very good presentation and I just want to say to you what this is all about. Bempedoic acid, actually, is basically an agent that blocks-- in the synthesis of cholesterol, there are a number of enzymes that work from top to bottom-- it's cholesterol synthesize.
Actually, statins are in the bottom. But this one is on the top. It actually blocks part one of the enzymes. And this was the approach taken by the industry. The industry, actually, what is doing now is addressing the different enzymes of cholesterol synthesis. This is basically the approach it is taking. Statins were so successful, and the question is, if we block this proximally, is this going to be more successful?
That's what really has been the industry in the last few years. Well, here we are with this bempedoic acid in patients that actually have significant LDL cholesterol that cannot be addressed properly to the levels that we would like. These are patients with familial hypercholesterolemia or patients with a very risk in which statins were given or other agents were given and they didn't reach an LDL cholesterol basically below 100 mg/dL.
Okay? And this is actually what we are doing with the PCSK inhibitors. Really what we try to do is to really go into patients that are treated with such agents and statins and so forth and we cannot reach the levels that we would like to. So this is here. It reminds me to the ezetimibe story, in which it really came up very borderline on the first study, less borderline later on, but we will comment on this.
So these patients were high risk patients and many of them, over 50% actually, were patients with familial hypercholesterolemia. And basically, as I mentioned, the LDL cholesterol levels did not reach the appropriate level with the statins and otherwise. Statins were used in 80% of the patients, not in other 20%; they didn't tolerate statins. So not everybody was on statins, but they were in some kind of lipid modifying agent.
The mean baseline of LDL was 120 and the reduction in LDL cholesterol to go to the bottom line was actually about 18 to 20 mm/dL. Okay, so if you have a LDL cholesterol of 120, it got into about 100, 105. This is the type of thing that is important. It's exactly like ezetimibe. When ezetimibe came into the market, the results were not so striking.
You know, to reduce this type of level is not so impressive, but when you add this to other drugs that have done the main job and you drop 20, maybe you achieve something. But let me tell you about this story of ezetimibe because it's very interesting. When the study came out, the first study, actually it was not too exciting like this one. When ezetimibe was looked at the number of events that actually you prevent in a follow up, then it became very significant.
What I am saying is, a comment I can make about this study is that when we judge trials, it's very different to judge the first event, which is most of the trials they do, and this is bad because it's short term, than to judge subsequent events if you have a longer follow-up. So I think the lesson of ezetimibe, and the lesson of this particular drug is that we should really look at trials longer than we can. This is common sense.
But just trying to look at how many events are really prevented in the follow-up. And when you read the literature, I think this is very, very important. Because you may see something that is trivial on looking only at the first event with a very short term follow-up, and you have to really wait whatever pharmacologic agent is in the long-term follow-up. So this is basically thoughts about this study. Now, there was a little bit of a skepticism about this particular approach, bempedoic acid.
They say it will be very expensive and so forth. I don't know about this, but, you know, the concept of attacking the pathway of cholesterol synthesis, I think is a good one. And I wouldn't like to be critical here because the results are not so, you know, so good, but there is one issue that perhaps is important also to portray here. Let me give you an example. If today we had patients with heart failure and we only had beta blockers, all the rest that has been discovered is out, beta blockers would be a great winner.
If today you have a study in which you have all the aldosterone inhibitors, the ACE inhibitors, the receptor blockers, and you add beta blockers, you would say, you know what? Not good. This is the reality. So I think what is happening is, at the moment that we affect a biological pathway, more drugs that we give, less will be the effect. So I think these new drugs that are added to other ones, we always should think, maybe something that we will have to add, but they are not doing a good job, I think this drug alone, without the statins, the results would have been much more significant.
And I think this is a biological concept, very important at the moment that you actually review papers also. And this is why these studies in a way are important by themselves but also bring to us the concepts, new concepts of how to review the literature and how excited you may be or not be with a particular piece of information. So this is for this study. The bempedoic acid, alright.
I'm not doing too well. If you really look at the timing. But you know what? Let's try.
Segment:6 Discussion of DECLARE-TIMI 58 Heart Failure Outcomes.
The next one is exciting. All of them are having something as I said. Okay, here we have "Dapagliflozin on heart failure and mortality in patients with type 2 diabetes." This is a paper presented from the TIMI group, Dr. Tozak Kato from the Brigham and Women's Hospital.
And let me go back to the original study. You might recall the DECLARE-TIMI 58 was one of the key studies in really looking at the SGLT2 inhibitors in patients with diabetes. Let me see if I can go to the original study, I hope. Yeah, here it is. The DECLARE-TIMI 58 was a randomized double-blind multinational cardiovascular outcome trial comparing 10 mg of dapagliflozin with placebo in 17,000 patients with type 2 diabetes with either established atherosclerotic cardiovascular disease or multiple risk factors for cardiovascular disease and a creatinine clearance of more than 60.
The emerging data of the benefit of SGLT2 inhibitors on hospitalization for heart failure was certainly something interesting because the results were good, as you know, with all these agents, the data is showing that hospitalization is decreased, heart events are decreasing, including mortality. But what is interesting is hospitalization in the original studies was decreased hospitalization for heart failure. It was the most predominant reason for the hospitalization of these diabetic patients.
And this didn't fit with the way that we think this drug worked, which is basically they prevent reabsorption of glucose and sodium in the renal tubules. You drop the glucose levels in blood, but what this has to do with heart failure? And this is a question that is not resolved and I don't know if we're going to waste time here. But what happened is, one of the sub-studies of this DECLARE-TIMI 58 was to look at heart failure specifically.
And this is what was presented in this meeting. I mean, the good news is they choose patients from these 17,000 who had heart failure with reduced ejection fraction, which was only 3.9% of them. And then they choose patients who have the other type of heart failure with preserved ejection fraction of about 7%. And then the other 88% of the patients, they didn't have any heart failure.
But they were part of the study so they were all followed. And what they basically found is that most significant finding was the reduction of hospitalization for heart failure of some of the patients that were on heart failure before, particularly those with reduced ejection fraction. And some of the patients, they were not on heart failure but they really were hospitalized with heart failure after a period of four years of follow-up. So, basically, what the study is showing, is that dapagliflozin in the randomization scheme with 10 mg in patients with type 2 diabetes really had an impact on heart failure.
First, particularly in those with reduced heart failure from the beginning and those who were hospitalized with reduced heart failure at the end. What about this study? Well, there's a big thing in the way it was presented. This is the first study done on SGLT2 inhibitors in heart failure. I would be very, very careful on that because this was not ad hoc. The study was already, from the beginning, they were going to look at this. But on the other hand, it was not a study on heart failure, instead picking up a group and trying to do the best they can from the original group of the DECLARE study.
So there are at the present time, in my knowledge, five studies with these drugs on patients who have heart failure from the very beginning. And all the patients that entered are patients in heart failure. And they're using these in heart failure with preserved ejection fraction and in heart failure with reduced ejection fraction. This is the first approach, but certainly, it's not unique in the way this study was actually designed.
Segment:7 Discussion of WRAP-IT Trial.
Antibacterial envelope to prevent infections of cardiac implantable devices.
Well, this is the story. And some people made this story dramatic, some not. Okay, what is the incidence of infections of these devices? And we are talking the cardiac implantable electronic devices, all the kinds that you know. It's actually 1% to 2%, so let's be sure that we are not talking about 25% infection rate and so forth. It's low. The problem is that once you get the infection, the morbidity and mortality is very high, so this is not the kind of people you like to see.
Because the outcome's are not good. I think that is important, but not the incidence. So with all of this in mind, the study actually evolve, this so-called WRAP, W-R-A-P-dash-IT. The WRAP-IT study, which was presented by the Cleveland Clinic group, Dr. Khaldoun Tarakji was the main presenter. So, let's see how the study was designed.
Well, basically, this was a randomized controlled clinical trial of near 7,000 patients. So here we really have a large group that underwent these procedures. And then what happened is the patients were randomized into one group that they have an antibiotic diluting envelope and let me say to you that this antibiotic was the-- let me see, I have it here, was a combination, I think of rifampin.
Yeah, rifampin and minocycline. And it was in an envelope with the device. And this antibiotic was actually absorbed and finally disappeared in a period of nine weeks. So, it's a process at the very beginning of the device. And then the question is, what about the results? And the results were actually very positive. Just the bottom line, 40% reduction on the primary end point, which was infections, and also some reduction in other comorbidities that happen with infection.
So, in fact, there were 25 patients in the envelope group who develop infection, and 42 patients in the control group. So the results were striking. The total follow-up I will say was about 20 months. And certainly, is a way to go. There were some issues that actually were discussed, and that is, this is the first consecutive patients that the issue is being addressed, but apparently, the patients were not-- the question is whether were consecutive or not?
With consecutive, it said that only one manufacturer of a device was involved in this study. So there was only one manufacturer. So it's a consecutive study, only with that one device from a particular manufacturer. So this has to be opened up to others and so forth. But it seems it's positive in the way that this is being approached. Now, the next one, the 8th study that I'm presenting here,
Segment:8 Discussion of Coronary Angiography after Cardiac Arrest without ST-Segment Elevation.
is the patient with cardiac arrest.
This was the study from the group in Amsterdam, Dr. Lemkes presented it. And it's a very simple study. Actually, these are patients who, 552 patients, who had cardiac arrest without signs of STEMI. Patients with cardiac arrest and STEMI, we know they need an angio, there's no discussion. But here, the question has been, are all these patients with cardiac arrest, they have to be rushed into the cardiac catheterization laboratory for an angiogram?
Well, the patients were randomized into, pushed to the cardiac catheterization laboratory versus another group that was done later after the neurological evaluation and so forth. And just to tell you the results were exactly the same. The survivalship at 90 days of both groups was actually 65%. So basically, the message is that when we have a cardiac arrest and the patient is not STEMI, there's no need to rush.
Do the right things, whatever the things are. And then the patient may or may not have an angiogram. This is the bottom line of this study.
Segment:9 Discussion of STOPDAPT2 Trial.
And then we get into one very surprising one, which is the so called STOPDAPT. Stop it. STOPDAPT-2 studies came from Japan, Dr. Takenori Domei present this study, and it's very fascinating how this study's being introduced. The study's being introduced saying that what we are talking about DAPT is without data.
It's so much data on DAPT that when I read the introduction, I said, "This is funny." What they are really saying is that the concept that we should do, we should use two platelet inhibitors for whatever period of time, six months, a year, or for the whole life, they say there is no good background that this is right. Because when you use the dual antiplatelet therapy, is you have a problem with bleeding. And the background intents of decreasing incidents of ischemic events is not clear.
I was surprised by this, but this is the introduction of the paper. Well, they really move on, and they had 3,000 patients undergoing stenting, of one kind or another. And the patients' randomization was interesting. They used one group, clopidogrel and aspirin all through one year, and the other group, they used clopidogrel and aspirin the first month, and they stopped aspirin, okay? That's basically the issue.
And I now go into the bottom line. No question, that the bleeding was significantly less in the group that was clopidogrel one month and then-- Excuse me, clopidogrel and aspirin one month and no aspirin afterwards, compared with the group that did two antiplatelet therapy for one year. And what is most surprising, this is very surprising, I don't know what to say, the incidence of ischemic events was the same.
And actually, if you look at, maybe it's even better, with the group of one month of just two antiplatelet therapy and later with just clopidogrel alone. I think one of the questions that I have to be sure here is about what is the-- what is, I think was clopidogrel, yeah, it was clopidogrel the drug they use-- great surprise. Japan, 3,000 patients, and this is the data.
People were stunned about all of this because it really goes back to the concept of dual antiplatelet therapy. I must say the following. And this is why this paper has to be written. What we have is the slides. What kind of patients we are dealing with? I am assuming these are very low risk people. They didn't have acute coronary syndromes, they have no tendency to bleed, rather young-- I am guess making it.
Because here it's not. I don't have any idea. So I think we have to be very, very careful in just taking this paper like dogmatic because I think they are dealing with a population that is not clearly identified in the way it was presented. So, we have to wait. Let's use dual antiplatelet therapy and continue to struggle how long we give these drugs, rather than just using this. But it's interesting.
Segment:10 Discussion of the Ticagrelor Reversal Agent.
Now we have two papers that were not part of the presentation, but I think it's worth mentioning. The first one is the following. Is the ticagrelor. This is a study that was presented by Deepak Bhatt from the Brigham. And it's a randomized study of healthy people. The number of volunteers is actually only 64. And they were randomized in intents of using an antibody which is an infusion, the so-called PB2452.
48 of these people and 16 were on placebo. This is a tough thing to be a volunteer, I don't know how much they pay these guys but it's an intravenous bolus and prolonged infusion 8, 12 and 16 hours, so it's a real issue. Anyway, these patients were all treated for 48 hours with ticagrelor. So that's important. And the results are very striking. You know, this is obviously the first approach of a phase 1 of a study, but certainly the drug was blocked by 80% by different platelet inhibitors, I don't want to get into the detail, it was blocked very rapidly over a period of two hours.
And this is very interesting because the question is, how do we work today when we have patients in trouble? Well, basically, we give platelets in many of these patients. The problem with this drug, ticagrelor, it moves freely in the plasma, so whenever you give good platelets, it gets there. With the others, do not. I think this is very important because we use platelets. But remember, ticagrelor is very unique because it gets attached to the platelets we give, so this is not the way to approach these patients.
Well, as you know, patients who have a tendency to bleed, they bleed, we have to stop ticagrelor for three to seven days, even to do bypass surgery and so forth. Here's a situation which is quite interesting. However, let's be careful. These people were healthy people, so we don't have any tendency to bleed, any bleeding that happened, what happened when we give this drug and there's bleeding with ticagrelor, we don't have any idea.
So I think it's an opening door which is quite fascinating in the reversibility of all these drugs, the NOACs, and all these drugs that we are giving today. The field is advancing, and I think very soon, we'll have drugs that will able to block all these new agents, antithrombotic agents. But I think I would be very, very careful not getting out here and saying we already have a drug for ticagrelor. There's a long road to do that.
And the final presentation is the primary prevention guidelines.
Segment:11 Discussion of the New ACC/AHA Guidelines on Primary Prevention of Cardiovascular Disease.
It's called "Primary prevention of cardiovascular disease." Now, there are few issues that I think are of interest. Maybe a few questions. And that is, the first issue, there's a paradox, and I will tell you the paradox. They say, "The most important way to prevent atherosclerotic vascular disease, heart failure and atrial fibrillation is to promote a healthy lifestyle throughout life." Fantastic statement.
I mean, we are all in agreement. But now comes the second statement. "You should begin to work at age 40 to age 75." and what in the world is this about? All these guidelines of primary start at age 40. My friends, this is a problem. This is the problem of prevention today. The problem of prevention is we start talking when people begin to have events.
Or even a little bit before. I talk about children and nobody knows what I'm' talking about. They say this guy is crazy because he's a cardiologist talking about children. But I will tell you one thing. This is the problem with all the guidelines. We go there too late. And let me add more. All these Apple, great studies. the great studies by IBM.
all these studies that you see start in adult age. They are mentioning thousands of thousands of thousands of proteins and genes at some adult age. What is going on before? Even what goes on with the mothers who are exposed to thousand things that have effect? So what I'm saying is I take advantage here to at least present to you my passion about the whole issue of prevention. Unless we go earlier and earlier and earlier, I think we are wasting time.
I think this is great. What else can I say? Anything that has to do with prevention is worth it, so I say this is well. I certainly, I don't think I will read it because no people really don't, I may go do some things. How to stop smoking, you know, sure, we can go to all of this, but the bottom line is that, we have to think about prevention. And this document, I think that's that. And I am completely in favor of, but the question is I think we are starting too late.
Well, thank you very much for your attention. This is what I learned on this meeting. I say that's good. It touched a little bit of everything into our field Thank you. Alright.
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