Dr. Dominick J. Angiolillo, Medical Director of Cardiovascular Research at University of Florida Health discusses antithrombotic therapy in patients with atrial fibrillation undergoing PCI. He elaborates on patient risk, pre-procedural considerations, and the European vs. North American perspectives.
Related Links: Twitter @PennMDForum Cases of Functional Mitral Regurgitation Teer Options: Part 3 Functional Mitral Regurgitation: Part 2
Yeah. Mhm. Yeah. Yeah. Yeah. All right, good morning everybody. Welcome to cardiology. Grand rounds Today. CMI code is 70672. Again, that's 70672. We'll make sure that that's in the chat section as well, so you have access to the code and we'll announce it again at the end of the talk. Similar to prior grand rounds. Please feel free to leave any questions or comments in the either the Q and A. Or the chat tab and we'll leave the last 10 15 minutes um for a Q. And a session. So give everybody another minute or so to to log in and then I'll introduce our speaker and we'll get started Again. The code for today is 70672 for those logging in on the telephone. All right, well, good morning again everybody. It's my great pleasure to announce our speaker today, dr Dominic and really low from uh from florida Dominic received his underground and medical training in Rome Italy. He did his training at various sites in spain and then throughout europe And then joined the University of Florida in Jacksonville in 2004. He's an interventional cardiologist there, it's very involved with their cath lab with their fellowship program program and has really been a leader in the area of anti platelet and anti thrombin attics and cardiology. He's been involved with multiple studies, looking at anti platelet agents, has been very involved with the development of anti platelet agents and lately has really done a lot of work in terms of guidelines and recommendations on how to appropriately treat patients with coronary disease with atrial fibrillation um and a combination of those. So we're very excited to have him speak today on this topic. It's something that all of us deal with on a daily basis, especially in folks that now tend to have a lot of coronary disease and atrial fibrillation overlap between the two. So Dominic welcome to penn cardiology. Grand rounds virtually. We appreciate you joining us and we're very excited for the talk. I'm gonna stop sharing my screen and let you take control here. Well uh thank you Samir and good morning everyone. Are you able to see my slides? Not yet. Not yet. Okay so let's see here. Yeah. How about now? Perfect. Perfect. Okay great. Well good morning everyone and uh thanks again for for the invite and it is my pleasure this morning to speak to you about a topic that I've been working on now for many years which is that of anti from biotic therapy in patients with a fib undergoing P. C. I. And as you were already alluded to before this is a topic that many of us deal with on a daily basis and explain to you in a few seconds why. And uh what I'm going to do is provide you with some practical recommendations on how to a deal with these complex patients. So these are my disclosures. I do work with most makers of anti tom biotic therapies. So let's speak a little bit about the uh epidemiology of a fib and P. C. I. We know that a fib is the most common arrhythmia. The prevalence of a fib as we all know increases with age. And we all know that we're seeing more and more a fib because not only are patients living longer but detection systems for a fib have also improved. What we also know that uh a fib and coronary disease have a common underlying risk factors. And this is the reason why is the second number of patients with a fib also have coronary disease. And many patients with coronary disease also require revascularization to the extent that the current metrics right now in the United States and in europe, is that around 8 to 10% of patients with a fib undergo PC. I. These numbers may vary according to your geographic location. So, for example, in florida we have a lot more elderly. These numbers may be a little bit higher. Certain asian countries in particular, Japan and south Korea, where the prevalence of a fib is a little bit higher. Uh Around 15% of these patients may require a P. C. I. So very, very common a problem. Now, what do we know about the treatment of a fib MPC? From an anti, from biotic standpoint? Well, in terms of uh patients treated with undergoing PC I treated with stents, uh we know from a number of trials conducted mostly in the mid nineties that dual anti platelet therapy is the treatment of choice. And we know that dual anti platelet therapy is better than or atlantic regulations. On the other hand, in patients with a fib, we use anti from biotics to prevent cerebral vascular events and we have very clear evidence that oral anti coagulation is better than dual anti platelet therapy. The problem becomes when you have patients with both a fib plus PC, who therefore may require, on one hand, dual anti platelet therapy. On the other hand, oral anti population when you combine these means this means triple and triple antibiotic therapy. And one thing that we know from about triple therapy, you don't need to be a rocket scientist that as if you as you add on or stack on therapies, there's an increased risk of bleeding complications and bleeding is bad. We now have many studies to clearly support that bleeding is associated with worse prognosis, including increased mortality. Now the fields gets somewhat complicated by the fact that we have several oral anti crime. And so in addition to a vitamin K antagonists now we have four no X. And in the field of dual anti platelet therapy. In addition to aspirin, we have three oral P two Y 12 inhibitors. So we have a lot of agents that can be used can be used in different combinations at different doses and I stopped at different time points. And this is the back of the envelope uh assessment of different combinations that we can come up with when we're looking at anti from biotic regimens for patients with a fib plus Pc. I and as you can see we as interventional cardiologists can become very, very creative. We have nearly three million different combinations. If you look at all these drugs put together, that's a lot of combinations. And so the question becomes, can't we create a framework to try to provide guidance to the interventional cardiologist or to the practicing clinician on how to best manage these patients. Now, approximately 10 years ago, a little bit more than 10 years ago, um we decided to put together an effort on behalf of a number of key opinion leaders from the U. S. And Canada to to this topic. And the reason why we we approached this was if you look at the guidelines and now I'm going back into years 2006, 2007. Uh the guidelines made zero mention about this topic. There are also not a lot of studies. And as you all know, the guidelines typically tend to be silent when there is a data free zone. And uh we learned from our experience from our european colleagues who also had the same issue and started put together some type of guidance, uh expert consensus guidance on how to manage these these patients. So we initiated initiated the same endeavor here in the United States. I'm not going to give you the whole historical overview of the past uh 11 years actually of recommendations but dive into directly the most recent recommendations uh that were published uh just a few months ago in circulation, which really is the best evidence based document that we've had today uh does thus far on on this topic. So what we decided to do uh in this in this doc documents is provide true practical recommendations. You know, many times you pick up a guideline and you pick up a review article, there's a lot of information and one is left with the question. Okay now what do I do? Okay so what we wanted to do here is really take the patient with this critical condition and work our way through in a very pragmatic matter and define what are the pre procedural considerations about this individual? What do we do during the procedure? And what do we do after the procedure? With an emphasis on uh anti robotic management for their a. Fib plus PC condition. So I'm gonna walk you through this and hopefully this will be informative also for the trainees uh on the line on what to do in your clinical practice and also to impress your attending. So pre procedural considerations very very important. Point # one. The fine appropriateness of the PC procedure and stratification of the patient. Why do we believe that defining appropriateness is important? Now a number of years ago the appropriate criteria for PC. I came out. There's been a few iterations of this. But to make a long story short, what I always explain to uh to my fellows, particularly when you take a patient who's gonna require oral anti problem therapy. Plus anti platelet therapy. By definition, when we put a stent in this individual, we are increasing that patients risk. So you need to be sure that performing the PC. I procedure, particularly in this individual is appropriate. We should be doing it regardless, but particularly in this patient, as I always say, when you put in a stent is a point of no return and the appropriate criteria are pretty well established. And what I tried to explain to my fellows again, you have a patient with critical scheme Yeah. With an acute coronary syndrome. For the most part these patients and these patients performing PC is appropriate if you have a patient with uh a lesion in the diagonal branch who was asymptomatic And Cameron 10 minutes on the treadmill. Probably not that appropriate. one may say why is that patient on the cat lab table for the first place. But again, we need to be considerate that once we put in a stent in that patient as mentioned before, we increase the robotic risk by definition because we are putting in a device but we're also increasing the bleeding risk because we have to stack on antibiotic therapies right now definition of risk and particularly when it comes to bleeding and ischemic and probiotic risk. And again, um providing this talk with the understanding that we're dealing with patients with a fib who have an indication to be on an or atlantic waggling based on the child's basket or now models to predict bleeding have been really really complicated. You see over the past several years we've had many, many models, and the truth is which one of these is the Is the best 1? Well we just don't know now fast forward. In a few years we've finally learned that specifically for patients with a fib the has bled appears to be the best score. Okay. The problem with the scoring systems, even if you look at has bled the accuracy of the score. In other words the C index Is around 0.6. What does 0.6 mean from a statistical standpoint slightly better than a flip of a coin? Right. And the truth is when you look at newer iterations of guidelines, these are the sc guidelines, but the same set for the uh for the A. C. C. Guidelines is we use has bled really not to determine whether we're going to treat a patient with an anti quagga. Um For example we're going to treat anybody regardless actually patients with higher scores. In other words high risk of bleeding have greater benefit from uh antique wagon therapy. So we have to come up with something uh something different. Now you may recall last year there was an initiative from the Academic Research Consortium which was that to define patients at high bleeding risk. And this was done because criteria were all over the place. And we said to ourselves let's get together group of experts from across the globe um together with drug regulating agencies. So we had involved the F. D. A. The european medical agency and the equivalent of the japanese F. D. A. And we came up with criteria to define patients at high bleeding race. Now I'm not gonna dwell too much on on on on these criteria essentially. We you need one major criteria or two minor criteria which are highlighted on the slide. But as you can see here by definition having being on atlantic regulation sets you already already at major risk. So everybody is at high bleeding risk. So it makes it very difficult to re stratify these patients. However, along the way a number of registries came out showing that there is incremental risk in uh in patients according to the presence or absence of a junked of major or minor bleeding risk criteria. So we said to ourselves instead of creating additional confusion with different bleeding risk course, let's just use R. H. B. Are by definition, we know that all these patients are at high bleeding risk and look at a dish presence of additional major or minor risk criteria. To further uh stratify patients leading risk. So very very simple. We also uh wanted to simplify the definitions of probiotic height, robotic and high ischemic risk. And you're probably asking what's the difference between height, robotic and high ischemic risk? Well, if you look at the at the guidelines, particularly our european colleagues do a much better job than the A. C. C. H. A. Guidelines which as you all know, are largely outdated. They define as high probiotic risk, standard clinical criteria for thrombosis. So A. C. S prior centrum moses and uh predictors of PC. I complexity. And we said to ourselves, well this is actually what we do in clinical practice, right? When when we're in the cath cloth. And although there's overlap with markers for high ischemic risk because typically patients with diabetes chronic kidney disease, there the one with complex PC. I we like we like to keep these two things a little bit distinguished because the high from biotic risk is what in our mind. Okay, what's in our mind when we put in a stent and when we're very concerned early, right about a stent thrombosis. The high ischemic risk is something that we think about more long term and may have implications for how we manage our patients uh down the road, for example, after after one year. So it's very very much in line with the most recent chronic coronary syndrome uh guidelines. And so we applied the same exact model. And again, this is to simplify this concept. So let's dig into uh some additional practical components. Procedural considerations. Ah I believe that regardless most of our patients should have radio access for their uh coronary interventions. Uh this is uh something that we should further emphasize in our high bleeding risk patients. And I believe that there's really no reason nowadays not to use a new generation drug eluting stent. Uh There is still a thought process out there that because the patient is on the oral anti population, uh one should be using a bare metal stent when you look at all the new data that's out there with new generation drug eluting stents there uh safer than bare metal stents. We now have dedicated trials uh in high bleeding risk patients with newer generation drug eluting stents. And there's also another ah aspect that many people don't typically speak about. A lot of our patients who are a fib who come to the Cath lab. They're by definition complex patients. I mean, I don't recall too many patients that I treat with with a fib who have simple coronary disease with a with a four oh where I can put in the four by 12 millimeter stent. Okay, these are typically more complex patients and we want to provide the best extents that we can also because keep in mind that if you do have instant restenosis or any type of stem failure related to the use of an inferior stent, then you're really in trouble because you need to be a little bit more aggressive down the road with uh with additional stent implantation, again, further enhancing the tram biotic and bleeding risk of that patient. Now, a very practical question that pops up is what do we do uh in our patient who's on chronic oral anti population, who needs to come to the Cath lab. And this is something where uh on the north american side, we differ from our european european colleagues now on the north american side uh In general in general we favor uh when possible uh huh Having a washout period before the patient uh from from the atlantic problem before the patient comes comes to the cath lab and again I repeat when possible. Obviously have a patient with acute coronary syndrome or coming with a stem. You've got to bring the patient to the cath lab. But in your elective cases uh our recommendations and this is also from the A. C. C consensus is really to have that washout period. And the reason for doing so is due to the fact that it's not a problem doing a heart cath on the patient while on orlan tech wagon particularly you're going from a radio approach. The problem becomes if you need to proceed with an intervention, what's the anti problem regimen that we need to give to that individual? We just don't know right because if they're on treatment and you're adding parental treatment in the lab, uh these are very high likelihood of overdosing and overdosing is is not necessarily a good thing. The other reason why we, on the north american side believe that there should be a washout period is very simple. Most patients, most patients with a fib aren't, you know, acting nowadays. The truth is, and the vast majority of patients, and the only exception are those patients on the bigger trend who have renal dysfunction with one day of washout from treatment. You've eliminated effects of the drug because no, it's have a very fast onset and offset. So it really isn't a big deal. It really isn't a big deal. So if your schedule on a patient for an elective procedure just tell him not to take their new york's the day before. And I'm pretty sure that uh all of you turn yourself in a situation where uh patients come to the lab and uh whatever reason uh patients did not stop there atlantic problems or they're coming from the floor, obviously always the fellas fault, right? Because they did not do it. This does happen and in that specific case, Well, there is some recent data that was just just published and this is where this editorial is taken from uh showing that okay it may be safe. Okay. But again, I strongly believe that it would be preferable to have that washout period. The anticipation for example, coming in with a non stem e uh the recommendation is to give additional happen as as a bridging strategy, but otherwise uh again with the no tax, no need to uh no need to bridge our european colleagues instead say bring the patient to the cat lab. Um if there I. N. R. If they're on the vitamin K. Antagonists and their I. N. R. Is above 2.5, don't give additional anti regulation. If less than 2.5 give your uh give additional anti coagulation. Well for all patients on a no ac just give additional anti coagulation. And I'm I don't agree too much with this approach. Um Again if needed, we do it, but again not my standard of care, I'm not gonna spend too much time on this slide and what we do in the cat lab. I believe the vast majority of us have gone to a strategy of going using a good old fashioned um fractionated heparin. This is what most of the trials have been done with. We do uh indicate that you can consider by Valley Ruden in a patient who may be at high uh bleeding risk. And in general we tend to uh not use the more potent uh anti platelet agents such as GPS in candler but do give a preference to Kangol or if needed simply because of its uh more favorable safety profile. So this is the heart of of of our of the recommendations that would like to highlight uh these recommendations are now uh 100% almost 100% in line with the A. C. C. Consensus documents as well as the E. S. C. So I'm gonna walk you through this um and uh kind of uh explain some of the key uh practical recommendations. So you see here we indicate what's the false strategy in the fall strategies that everybody uh receives aspirin plus the P two Y 12 inhibitor plus the atlantic private during the Pc. I. Period. And what do we define as perry pcs? What you see here? It's the inpatient stay until time of discharge or a few days longer. Up to one week. Post pC. That's the definition of para PC. Now we just didn't come up randomly with this definition. There's a lot of thoughts on how we came up with this and it stems from from the clinical trials and I'm going to get back to that in a few slides after this para PC period. The recommendation is to stop aspirin and continue double therapy. We're in atlantic Parkland and a P. H. Y 12 inhibitor preferably clopidogrel up to one year and that one year drop all anti platelets and stay on the Orlando like wagon for patients considered at high from biotic risk. We make you may consider prolonging triple therapy up to one month. But categorically we do indicate to stop aspirin at one month. Do not continue triple therapy beyond that. And then same recommendations If you have a patient particularly high bleeding risk, we say, well, you know what all the dap safety data or say that you can stop that early. Well why can't you do the same concept with double therapy and therefore consider stopping all anti platelets at six months if you have a patient at high bleeding and low ischemic risk. So how do we come up with these recommendations? And again, this is how all other guidelines come up with these recommendations? Well, first uh ah component is why is a no act the oral anti crack glint of choice? Well, it stems from clinical trials we have now for our CTS Using all four no axe and I'm not gonna spend too much time because they all say the same thing is that a strategy of double therapy within no ac plus a P 2012 inhibitor is better than the strategy of triple therapy with a vitamin K antagonists consistently across the board. When you look at meta analysis, you can see that production in bleeding, but what's important? Also a significant reduction in intracranial hemorrhage. One of the questions that comes up is, you know, which knock do we choose? A lot of confusion. So there's a lot of information on on the slide and I'm going to try to summarise for this. First of all, there is not a no ac of choice, the same way we for a fib in general for a fee plus Pc, there's not a lack of choice. There aren't any head to head comparisons. So you choose what you believe is best for the patient and the patient's already on a no, it makes no sense to switch right? If you need to start a no act well. Sometimes there may be physician preference access in my opinion is the most important thing. Right? Uh, so pretty interesting that picks up and will soon become a generic uh whether you want to give a one stadium or twice daily. Uh, no act. Okay. So uh so again there we cannot recommend one agent over another and generally prefer not to switch. Now the patients and the vitamin content agonists many times. That may be a reason to switch the patient to in Iraq unless the patient has a contra indication to be on a knack. For example, patient moderate to severe mitral stenosis or mechanical mechanical valve or left ventricular promise. Although many of these patients we are using we are using no ax. Okay, mm. The second question is dozing. So you may recall over the past 10 years everybody came up with their own dose of a no act. And in all the trials, it was pretty clear you use the stroke prevention those very simple. The only exception which was done in the Pioneer A 50 Pc I trial is using rural Rock Saban at 15 mg instead of the 20 mg. The important thing is that if you do use the 15 mg on top of an anti platelet. when you stop the anti platelet, you need to go back to the full Regimen of 20 mg. Otherwise, just keep things simple. Use the stroke prevention dose as you would use routinely in your clinical practice with those corrections based on FDA indications, for example, patient with renal dysfunction, bodyweight etcetera etcetera. If for whatever reason, uh, there's a patient who cannot afford in Iraq uh and you need to use a vitamin K antagonists. You need to target the I. N. R. 22 point oh 2.5. And then this is based on registry data that as soon as you go above 2.5, that's when the patients bleed. Yeah, we discuss the anti craggy island and I'm trying to go slowly here, particularly for the trainees on the line. Let's discuss the anti platelet component. And you can see here, based also on my prior slide, that single anti platelet therapy needs to be started as soon as possible and we prefer keeping single anti platelet therapy, would have P two Y 12 inhibitor over aspirin and otherwise drop aspirin. Now again, for the Trainees on the line, you may say why drop out from to keep AP two or 12 inhibitor? Well, it's very simple for those of us who have been working in in in in the field for for for many years, we know that using a P two Y 12 inhibitor is critical for our standard patients. Okay, It's pivotal and why? Because P 2012 modulates platelet activation and modulates platelet and qualification. And we have trial data to show that Pete Y 12 is critical in reducing arterial from biotic events. So if one thing needs to go, it's going to be aspirin. And the trials support that. Now. For those who are a little bit skeptical about dropping aspirin, I say, hold on a second, let's go back to basic concepts of uh anti traumatic pharmacology because dropping aspirin does not mean completely eliminating anti storm biotic ethics. This is for two reasons. One we still have a P two Y 12 inhibit on board. And too, let's not forget we have an anti fragment and an antique wagon not only blocks obviously, craig relation factors, but by modulating thrombin. Right, brahman is the most important producer platelet activation and so therefore you also have anti platelet effects extent. As you can see over here, there's synergism between oral anti progress and anti platelets. And if there weren't that synergism in all these trials that I just showed you where as you can see from the slide in three of the four trials, the mean duration of aspirin therapy Was 1- two days. We would be seeing sent thrombosis all over the place and that was not the case. So, the reason why our definition of para PC I period was At time of hospital discharge. In general, 1-2 days up to one week is taken exactly from these trials. You see the mean Time to randomization was 1-2 days and three of the four trials and in one was around one week. So that's what we did. Again, when we look at the studies, significant reduction bleeding, no increase whatsoever. An ischemic endpoints, there was simply simply numerical increase in stent thrombosis which was not significant. Now, the problem with stent thrombosis is that this is a very, very rare phenomenon. Again, when we look at other data, this is another man analysis coming from our group and you can see here again, no difference whatsoever in ischemic events Signify 50 relative risk reduction in bleeding. And when you look at some of the ischemic and points for example stroke, they were actually reduced uh with the uh dropping aspirin strategy. Now obviously ah we're all very concerned with dropping aspirin uh what stent thrombosis, right. And that's the reason why we very specifically, if we called the beginning of my presentation, we define, We distinguish between symbiotic risk and ischemic risk. We know in all the studies, 80 of stent thrombosis occur within the 1st 30 days. Okay. The vast majority of them rates are very low. I think we want to give a rough No 1%. Okay. one is very low. When you look at the trial data and there was a trade off analysis coming from the Augusta's trial, it was shown that if you keep triple therapy Up to 30 days, you're going to slightly reduce the symbiotic events. You're going to increase bleeding by definition. But it's called a trade off. So there's almost a wash. Well, one thing's for sure That after 30 days if you continue triple therapy, you're not gonna get any benefit in terms of s chemical event reduction and you're only going to get more bleeding. And that's the precise reason why not recommendations. We say the false strategy stop aspirin during the peri pc period. And we gave the definition. If you have a patient who you deem at particularly high traumatic risk, you may consider triple therapy up to one month but do not go beyond one month. And again once you've ruled out patient high bleeding risk the issue however, and one thing that we need to disclose is that this concept of prolonging triple therapy up to one month however has never been tested in R. C. T. This is extrapolated from Uh from uh from from the trial. Okay. We really don't know moreover who are these patients that are having sent from bosses? Because the event rates are so low it's 1%. The only way to really have a better understanding is if we do some type of patient patient level meant analysis and look at all these individual patients and understand who are they? Are they the complex PC. I patient? Is it because the stent was implanted suboptimal, are they the diabetic patients? We just don't know one concept that come up was are these patients to poor, poor, pitiful responders makes sense, right? Because if you're dropping aspirin and the patient on clopidogrel, which is the default PT 12 inhibitor and we know that there's an association between poor crippled a response and robotic complications. It could be but this was not tested in the studies. Now I recently um uh co chair the the international consensus on platelet function genetic testing. We do provide some wording to that extent, that it may be considered reasonable to do testing in these patients when you're dropping aspirin. Again, it's not based on any data, but if you want to do in your clinical practice, it's reasonable. The guidelines and our consensus documents. We're kind of silent to that extent. We say refer to expert consensus documents and this is what we say now. What we're doing here at university of florida is we have a program where we're doing genetic testing and in all our patients. And uh one of the things that we're doing we come up with a score uh to better enhance the accuracy of defining patients who are poor capital responders. Because again genes don't explain everything right? So we integrate jeans with clinical variables and this is the A. B. C. D. Gene score. And if you have a score above 10 then you may be considered at higher risk. Uh And we're actually doing a study where we are randomizing patients to continue with standard of care which is clopidogrel versus treatment with with A 60 mg dose regimen of of of Thai category. Again, it's a pilot studies but we're doing here um but uh again uh we believe a little bit more of using the genetic scoring because the only way you can define the patient of being with high platelet reactivity While I'm clopidogrel, the patient actually have to be on the grill. And if you believe that the patient may not be a good responder, why take that risk? So this leads to the question, Well, why not use the more potent P two Y 12 inhibitors? And you see in the trials over all, the use of the potent agents was somewhat limited. You see that the only trial that had more than 10 use was re duel, it was 12 I category. You can see across the board the use of press or grow, We're like in the one range. And that's the reason why in our recommendations. We do say yes. Clopidogrel is the treatment of choice. You may consider a potent P 2012 inhibitor particular taika galore. If a patient is at high probiotic risk, for example presenting with an axe and with reasonable reasonably low risk of bleeding. Another reason to consider to cog or is in addition to we have a little bit more data is that being a reversible binding agent uh has a faster offset. So if you have a bleeding ah I think it's a little bit more forgiven than prasugrel, which is an irreversible agent too. Let's not forget we're dealing with patients with a fit. Many patients who have had a prior cerebrovascular events which is a contraindications for procedural Uh and and and three although still under investigation. There is also now an antidote for for tech agoa which hopefully will be available clinically for everyone. So I think there are reasonable uh reasons to say why consider tie Coughlin. Why in general we don't recommend practical. Again I think practical is an excellent drug but perhaps not the best choice in these patients. And this is the best data that we have using Takata galore uh uh in this patient population. Uh And you can see that the data are overall consistent with patients treat with clopidogrel. But obviously the absolute bleeding rates are a little bit higher. We're gonna wrap up here is right on time with some of the post procedural considerations. Now you see here we do recommend close monitoring of the patient. And uh we recommend the use of P. P. I. S. And avoid non steroidals because these are essentially uh ways to minimize the risk of bleeding. But I'd like to focus here on the close monitoring and I believe as well as interventionists that we are a little bit more familiar with the data and and uh the cardiologist in general, we really need to stay on top of these patients. And for those of you who have your extenders seeing these patients in the clinic, right. We all have these goals that we have to see the patient, you know, 1 to 2 weeks after after the interventions. Uh I think it's critical in these patients. It's critical ah our rule at our institution if you have a patient uh with a with a fib when it goes pc. I was discharged for that reason. Also on triple therapy. Uh they need to be seen at one week because ah that's an important time to make a decision uh to stop aspirin if they have not stopped it already and explain to the patient because what to do because the classical thing that happens in real world clinical practice, you know, we're all crazy busy. Uh the you go to the unit and the turnover rate is really, really quick and people just don't take the time to sit down and explain things to the patient, patients. Very confused. Um They want to go home, we need the bed. It's just that continuing. So having that conversation that one week is critical and I do believe that it's critical that health care providers that are knowledgeable about the risk and benefits uh surrounding management of antibiotic therapy. Are those taking care of the patients. And I say over here, don't leave an exclusive care of the primary care providers. I feel sorry for the primary care doctors that they're dealing with all these patients. And they say, whoa, why stop the aspirin, Go back on the aspirin. And and that's why we have to educate the patient. Be very clear in our notes. I mean I've had primary have patients come to my office you know after a week or a month and I've stopped their aspirin or or whatever it is. And and the patient will tell me, you know, uh doctor a uh I know you told me uh to stop aspirin, but my primary care told me to go back on it, but not to tell you. And I'm like that's the primary driver of bleeding. Triple therapy, the primary driver bleeding. So again, I think we have to be very very clear in our notes involved very closely with our patients. Also these patients there their risk changes over time. Now, what do we do at one year? Well, as I mentioned before, we should need to stop all anti platelets and keep the patient on stroke prevention dose of oral anti regulation. With the exception those patients particularly high ischemic risk. And I provided you with the criteria and this is a lot of people confused. All right. So why do we why would we do that? Why we stopped the anti platelets? And the truth is when you look at all the data, you look at historical data, vitamin K antagonists showing a significant increase in bleeding and no ischemic benefit. And you look at more modern data coming from the Kelowna and their fire, same exact thing, no ischemic benefit, more bleeding. We're continuing uh an anti platelet on top of an oral anti quagga and therefore uh the recommendations from across the globe recommend to stop all anti platelets as I mentioned before there. Uh It's nice to see uh went on the two sides of the atlantic. We look at the data in the in the same way we look at interpret the data and in the same way our european colleagues for for years actually have been a little bit more uh pushing for prolonging triple therapy despite uh they've been ahead of the curve in terms of bleeding reductions strategies. And here you see the recommendations side to side from our european colleagues and north american colleagues. And it's interesting because these were developed at the same time With the two groups not knowing what the others were doing. And we came up with the identical recommendations. So this is very very reassuring As you can see here, Europeans as well considered as a default strategy. Triple therapy up to one week, so in hospital up to one week and everybody is same as ours, patients at high thumb biotic risk, consider triple therapy. Up to one month patients at high bleeding risk, considered the double strategy up to six months and then afterwards everybody stopped all anti platelets. So again virtually identical. So with this I will stop here and thank everybody for attention and happy to entertain any questions. Thank you. Alright, Dominic. That was fantastic. Thank you for the talk and I also want to just thank you for all the work you've done in this area without you and everything you've done. We would not be here in this state. I distinctly remember and I think most interventional lists and general cardiologist remember it wasn't that long ago where we had no idea what to do with these patients. It was every intervention list. Every cardiologist had their own regimen. It was a combination of Coumadin and aspirin Plavix um and became very confusing for patients and providers. So thank you for the talk and also thank you for all your guidance in this area. As some questions start to come in, I'm gonna start if you don't mind to pick your brain a little bit, just anti platelet agents in general and then we'll kind of hone in on the A. Fib patients specifically with dual anti platelet therapy. We know that there's a critical window that patients have to be on it. But we also think that there may be some benefit to long term dual anti platelet and while 6 to 12 months seems to be the ideal length for most patients. There are some that we do one month and this is regardless of if they have a fib or not. And there are some patients where we may extend dual anti platelet for several years, especially those that have diffused coronary disease or lots of coronary disease. What's your kind of approach to duration of dual anti platelet? And then we'll specifically talk about the fifth patient. Sure, sure. This is a great question and been another uh passion of mine. Uh and and um and I'll try to give a very practical and simple answer in general when I think the the european guidelines, both the CCS guidelines and the latest non stemming guidelines, they've nailed it and they got it right, okay. And so when we look at the all the data, all data pretty clear supporting the concept that when you prolong either dual anti platelet therapy or now even do a pathway inhibition because now we have that alternative using the basket of those were Iraq's banned. Um there is an ischemic benefit. Uh so what I do in my clinical practice is literally what the guidelines with the guidelines say. The guidelines now provide a class two a A recommendation that's extremely strong to a a it's the closest you get to class one for prolonging adapt or DP in the patient. Once you've excluded an HBR status, once it's really high bleeding risk. Obviously if they have multi vessel disease plus an enrichment factor and enrichment factors are diabetes, cKD prior my or peripheral vascular disease. So that's what I do in my clinical practice, the guidelines say give a class to be if only one of these are present. Yeah. So uh in my practice that I do have a lot of complex patients and and and uh my strategy is actually to prolong in many of these patients. Once I've excluded high bleeding risk, I have patients on that for years and years and years. The important thing is that you follow up with these patients and not just you know leave them on their own and evaluate their bleeding risk over over over time. The million dollar question is which is the best strategy to prolong with and um and the the guidelines. Uh Well the only guidelines, the extent of the european just provide the options but not provide the level of evidence with the different options. And the options do remain. The three oral PT 12 inhibitors. With exception with a category you go to the lower dose and the D. P. Strategy with the vascular dose. We are currently working on recommendations. Um So I've been invited guests with my with the guideline committee for the european society Cardiology uh to provide a better framework on level of evidence beyond that. So hopefully I address that question. Which ties into one of the questions that just came in through the chat ah Which I can go ahead and address, you know which patients warrant continuation of anti platelet agents after one year. It's an excellent question. And because which is the reason why we distinguish between from biotic risk and high ischemic risk. So after one year the strategy is kind of similar. So if you ruled out high bleeding risk patient uh and explain how we do that and you have these enrichment factors that I just explain to you. Okay so again multi vessel disease Prior am I uh diabetes ckd etcetera etcetera. Um then and the patient may be a little bit younger. Then the the tendency is to go towards pro keeping the anti platelet onboard and our recommendations to this extent is to continue with the anti platelet at the patient was already on which is in general clopidogrel. The important thing, the important thing is that you really emphasize with the patient uh not to start adding additional aspirin. The problem that we encounter in these individuals. Uh Is that what if the patient for example needs surgery and they want the patient stop the anti pregnant and they want the patients stop uh Lipitor girl says no don't stop everything. So that may be the only reason why. Okay keep the patient on aspirin because it just keeps things a little bit simple if they do require surgical procedure or something like that definitely if they do require one it's the time to just switch. But you know again if you're having your little old lady, what a fib gets us then 78 years old. Uh You know those are the patients who probably you don't want to want to continue because it's not about a matter of if it's a matter of when these patients believe mm a practical question for you, do you leave specific recommendations at the end of your cath? Report? What I mean by that is it can be very overwhelming to go through this. And as an interventional ist putting a four point oh by 12 millimeter stent in the mid R. C. A. Is very different than doing a complex bifurcation lesion. But maybe for the family doctor, the primary care doctor, they're not aware of those differences. So how specific are you in your recommendations? Uh I must admit we we tend to be pretty specific. Um but we also try to keep it simple. We ought to try to keep it simple. And I think one of the good things, the fact that uh this is what I always tell my hospital administration one of the beauties why you got what you need to support research is because they're also by definition uh quality measures and metrics because we really specify in the in the note because most of the patients end up in some study or something like that really what they need to do. And so I'm I'm I'm pretty picky about that and actually must admit the interventional cells. Uh they do a they do a pretty good job. I brainwashed him. They're not biased. Um, All the, all the stent companies are very excited about trying to get this 20 day or 28 or 30 day, basically one month indication for dual anti platelet therapy. Um what's your view on kind of that that short adapt or short anti platelet plus a an oral anticoagulant? Yeah, I mean, uh one thing that I did not spend too much time on uh during the call is we are where we are today because we have great stance. We have great, I mean, the safety profile is, is unbelievable. And I always, you know, tell tell my fellows. I mean you guys are spoiled. I mean, you don't know what we have to deal with a few decades back in terms of in terms of stents. So I actually support things. I mean the stent designs are, are wonderful and we have uh, um, you know, stent thrombosis of traumatic complications which are uh extremely low. I mean, you struggle to reach 1% struggle through 1%. Uh, stent failures in general are really well. So I actually view all these very favorably and uh, people ask me, um, also you think there's a better stent platform than than another. I honestly think you may have a personal preference. You may think that one stent maybe a little bit more deliver herbal uh, than another. But overall these are very, very good stents and many times as you very well know. Uh, Samir sometimes it's not your choice which sent you want to use it. It's your hostile administration who decides which tend to choose based on which costs, costs them, cost them less. But fortunately they're all very good. I think between the stents getting much better and I think our implantation techniques have really evolved better lesion preparation, a threat to me. We've got a variety of devices, inter coronary imaging. So all of this together I think has helped us absolutely. In the in the routine patient that has atrial fib for which there on an anticoagulant. are you doing 12 months of the anti platelet or 126? What's your kind of? Yeah, yeah. For the, for the most, for the most part I am I am sticking with the, with the 12 with the 12 months um, in selected patients, uh, I may go with the with the six. I'm also going to be very honest. Sometimes those who I end up going less is because of for whatever reason, even when they're on double therapy they may develop a bleeding complication. You kind of little bit forced to stop something, right? And and so your your hands hands are tied. Um I think we can do a better job in the findings were the patients who can stop even less than um Less than 12 months, for example, at six. But again, that's really a data free zone. And you when you look at the, some of the studies, it would be nice to understand some type of landmark analysis trying to understand between six months and 12 months for the bleeders. Uh, But some studies, for example, augustus which was the largest Didn't go beyond six months. So so um so definitely something that we need to work on a little bit better. What is your approach for either a proton pump inhibitor and H. two blocker? Um you mentioned a little bit towards the end of the talk. Is this something that every patient goes home on or do you have certain criteria? Yeah. So um if they're elderly for the most part they all go home on it. Um and the younger folks um a little bit at the discretion of of of the treating physician. Uh Generally it would be a P. P. I. Rate rather than an H. Two antagonists. I think that the P. P. I. Is just a little bit ah better to to to this extent. Again I'm not a gi doctor but that's what my G. I. Colleagues tell me. I'm not concerned about the that concerned about the drug drug interaction between um some PPS and Clopidogrel. Let's put this way uh ah Or my proposal would not be my first choice because there is there's a box morning and I'm as guilty as anyone because I did right the paper that went to the FDA for for the box warning. Um So it's not my first choice but for some patients it maybe represent the best choice when you look at the clinical data. Yes there is a farcical kinetic and for michael dynamic interaction. But from a clinical standpoint the data are not that strong for clinical uh interaction. So I may consider pento brazil or D. Excellent. As my as my first as my first choice. You mentioned a little bit about doing some P. Two Y 12 testing to help guide treatment. And this is always intrigued me for a number of years. And you know, a decade ago we used to check everyone's pr youths or the platelet reactivity units and then decide do we reload them? Do we adjust their P two Y 12 even genetic testing? But when you get to larger clinical trials, we never really got the benefit that we thought that we would. And maybe it's because stents or better, maybe it's because implantation techniques are better, maybe a combination of things. So I'm curious about how you guys came up with this protocol. And do you do rather than genetic testing functional testing ever. Good question. So um we've implemented a number of years ago uh genetic testing routinely our clinical practice. And it started off kind of little bit of an equality project. So the research was, can you implement genetic testing, routine clinical practice. And this was part of the Ignite program. Um and I believe that the pen was somewhat involved with this program and as part of the program was at the end of the five years, you need to be doing this routinely clinton. So now we're doing it routinely. Mhm. As part of the trial, however, that we're doing we do implement some functional testing but it's not our decision making. Our decision making is considering the genetic testing, integrating with um with clinical variables. And you are correct some of the earlier trials. Um We're not that convincing for tailoring therapy. And your comment is very, very timely. Just uh actually two days ago, uh we published in the Lancet results of a of a meta analysis showing actually how when you take all the data that's out there. A guided approach whether this is platelet function testing or genetic testing, Significant reduced mace, significant mortality, significantly reduce strokes if it was just uh stent thrombosis and reduced and reduced bleeding. So the problem, we were very excited about this. Again, I've only dedicated the past 20 years to it and so it was kind of rewarding to get this published in the Lancet just a few days ago. Um the problem with the individual trials, many of these are smaller, underpowered. Uh there has not been a lot of investment obviously from uh From the vice makers or pharmaceuticals to do the mega trial, like the 20,000 patient trial. But when you look at the data and inaccurate and I didn't present this here just for just to be focused on topic. I do believe that our recent data and some other recent data just published in Jack intervention may shift a little bit of thought process on how we may use. Consider functional testing uh particularly when it comes to potentially using strategies with these better stents. Do we need to go with such potent anti probiotic therapy? I think that's the key message. So um so time will tell we're doing it. Um Again we've been advocates for for it and we understand that it's not gonna be done routinely in all centres but this is what we do if you have time. I've got two more questions. Not uh a little bit off topic but because we have you I feel like I've got to ask you these questions. Um Your thoughts of pre loading with a P two y 12 for instance me recently in the guidelines there's been some shifting of thought of of whether that's safe and should be routinely done can get a clear answer. I don't pre treat. I don't I don't um and the reason being and uh you know, as you know, you should alluded to the recent sc guidelines. Uh now give a class three um for those going quickly to the cat lab. Again, it's very specific. And when you look objectively at the data, uh there hasn't been a single trial specific trial that supports show the benefit of pre treatment. Okay? We if we go historically and I'll keep a long uh answer short Cure to show a benefit. But the mean time to get to the catalog was seven days credo did not show a benefit. And plato everybody was pre treated. So it was not a randomization and try and nobody was pre treated. Uh and the coast there was harm and in dubious no benefits. So those are all the trials. So when you look at the ah the data as a whole, there really isn't data to support routine pre treatment. I do, however, get back to the at the institutional level if you believe is that's what's worked for your institution. And it's not an issue with your surgeons. And you think it's what's best, what your training program in which your er then that's what's best for you at our institution. It's extremely problematic. And we typically bring our folks to the catalog pretty quickly. And so my general rule of patients going to the cath lab pretty quickly from time Clinical presentation. And this is for example, 12, 12 hours less than 24 hours. And if you're doing non stem is on the weekend just deciding the cat lab being in the Southeast with a very high prevalence of diabetes and multi vessel disease. Some of these patients may go to surgery becomes kind of painful. Uh Then the washout so we put them on a kangaroo or bridge and then we send them to surgery. But this is our strategy. Mhm. The last question is recently some european data starts to question like Agra lures safety and true benefit over Plavix. Any thoughts or comments on that and kind of what's your P. Two Y. 12 agent of choice? Yeah it's not been a good past two years for technical for um So let's start off uh I mean uh we need to focus on the R. C. T. Which is a plato trial. Great trial, strong superiority over over of Chicago over clopidogrel things have changed a lot of these registries uh do have similar limitations. Uh This selection bias and what not. But I would agree with you that some of the recent data which may be driven by different patient profiles enrolled in the study. Better step platforms uh could could lead to uh less differential and benefit. Let's put this way between Chicago and clopidogrel though tech ago's particular beneficial and the medical manage patients which has nothing to do with the staff. So I think that changes in profiles of patient populations and stents could contribute to this um in the Cath lab. What do I do? I Again I typically in a. C. S. I always use a more potent P. To 12 inhibitor and if based on genetic testing or what not, we know that the patients are good responder. Uh If they cannot afford the drug we typical to clopidogrel. Uh I like to category in the Cath lab because if I'm using CANDLER there's no drug interaction and I like the fact that if I'm a believer in prolonging dual anti platelet therapy beyond one year, I can go from 90 to 60 mg uh of thai Cocula. But again, process is a very good drugs Show superiority. And the ice react. five trial. You may have your younger patient, big guy diabetic, uh doesn't want to take medications twice a day. You're dealing with the disease via. Process is a very good drug as well. And as a training program, I like to give my my fellows options to see all treatments. I'm not I'm not married to a single agent. I think we have very good options and I think I used my best clinical judgment based on the patient's in front of me, on which agent to choose. Okay, fantastic. Talk. Thank you again for for coming online today. We really appreciate it. And thank you for all your work that you've done in this field. We wouldn't be here today with Well, thank you so much and and great being with you and please all be safe. All right, you, too. Thank you very much. Thank you. Bye. Bye. Thank you mike.
