So, I think that the truth is, in the real world, things take a while to get in there, but also the data has to accrue and people have to understand and make decisions for themselves on whether to use it or not, and there's always culture change in a lab and those types of things. So, we're going to get to real world, but let's open it up to some questions. Benita? Yeah. Great talk. I just want to point out a few more details. You know, the first two trials were interrupted due to futility, but they also informed the third trial because the timing of the clopidogrel dosing was unknown whether or not to give it before or after, and so the ultimate trial that was done was based off of the timing of the clopidogrel, so it was given after…the load was given after in the kangalore arm, so there is…you know, the first two trials did help inform the design of the third trial. The second point is that there aren't any clinical outcomes data with ticagrelor, so that probably does put some people into a question. As you mentioned, there's only pharmacokinetic data. I will say that crushing ticagrelor is really great. Having them, you know, increase the absorption faster, you know, with taking advantage of the bucolicosa absorption is really great as well, but in practice, unfortunately, what some people do is that in the ER, they'll tell them to chew it, and then they'll give them a glass of water, and the next thing you know, all of the crushed ticagrelor is just being swallowed, and none of that absorption is happening in the mouth, so that is something to take into account in terms of how the pharmacokinetic data came into play. And then finally, 2b3a is a 2a in the guidelines, but not for routine use. As far as the class 3, it's a 2a for high thrombus burden, slow flow, no reflow. So there is still a place for probably both agents. Yeah, I found that it just takes away a lot of the concern in the STEMIs where I don't know what they got, and then obviously the field has moved towards not preloading patients in general, and so oftentimes these patients come in naive, and I worry that the thrombus burden may accrue during the case, and so I've been using a lot of cangrelor for that reason and understanding that we can stop it right away after the case and transition to ticagrelor. So I think that's where it started, and then I've been more impressed recently about the data. We're doing more CHIP cases, more CTO cases, and these patients have bifurcation stenting, complex lesions, calcified lesions, overlapping stents. So the stent thrombosis that we didn't see that much because of evolution of drug-eluting stents might come back to a certain extent, and this generation of cath operators are not used to seeing it as much, and so I think this may be a drug that could also help mitigate that in that scenario. Yeah. I mean, stent thrombosis rates are so rare to begin with. It's very hard to power a trial for that, but as you pointed out so well is that the mortality rates are so high, you know, when you do have it, so it's devastating when you do have it. So in those high-risk cases, it sort of makes sense. If they're not adequately preloaded, if for whatever reason you feel like there's not great absorption… There was a question in the audience. Yes? Hi. My question is, if someone's already been preloaded and adequately preloaded, particularly more the high-risk patients, MIs who can only preload so much, are you still giving Kangrelor and for how long would be my question? So… Let's hear from the panel what people are using, and then we can answer that question as well. So I think some of that will be actually addressed in my next talk that I'm about to give, but there is actually data for improved platelet inhibition within a shorter period of time, even when you do preload with ticagrelor, and the data on Pradegrel hopefully will be published in the next year. Yeah. I agree. I'm looking to be educated by Nadia about that. The question I had, though, for Benita and Kari was that there is one other indication that I know we did a hand-raising poll, and maybe it'll still be no hands, but where we've tended to use it a bit is in these patients being bridged for surgery. So they're on the floor, they've had a PCI usually within 30 days, but then they need a surgery, whether it's a cardiac surgery or other surgery, and you don't want it, and it has to be done. You don't want to interrupt. You end up having to interrupt a little bit, but you don't want to interrupt as much as possible. You don't want to have five days of waiting, and I don't know if you guys wanted to comment on that concept. I mean, oftentimes these drugs, as you get used to using them, you use them in situations that make a lot of obvious clinical sense, and we've done that, too. Someone with a STEMI, you have to put one stent in, you may want to bridge them to get them to their left main CABG that they need, and so you put them on the kangaroo, you don't give them the oral agent, and then you stop that on route to the OR. Are people using for bridging in that way? Let's show a hand, a set of hands, who's used it for bridging? That might be the largest indication right now, at least. You want to answer the question from the—so you answered, I think, someone from the audience, but how about chronic therapy, Nadia? If somebody's on it for a long time and their antipyretic inhibition is good, not being necessarily tested, but they're on chronic therapy, do you think you still get an added benefit from Ticagrelor in those high-risk PCI patients? Yeah, so definitely with Ticagrelor you do, just based off of the pharmacokinetic data, although it was mainly tested in patients who were just preloaded. I have not seen the data for Prasugrel, it may exist, but if anybody else got information on that, I don't have it in my offhand. Can I ask an operations question? Our system is early in its implementation and use, and I think a lot of folks in the crowd are probably wondering the same thing. When you're starting it in STEMI or when you're starting it in complex PCI, is it getting started in the ER? Do you guys have the ability to start it even in the cath lab? How are the places that are doing that? So we have it stocked in the cath lab and started in the cath lab, so the nurses are very fast, all are using it right away, and with our permission, obviously, at that point. And to answer your question, I'm not routinely doing it if I think they're adequately preloaded and no reason to think that their platelet inhibition hasn't gone, you know, so I'm not routinely doing that in that setting, and we started in the cath lab because starting it in the ER can get... Yeah, also you start it once you see the angiogram. I don't think it's, it's not necessary to start before that because the initiation is in two to three minutes. So you might as well take a quick look, see what you're dealing with and see whether you feel you need it, and if you need it, it's really within two minutes. Remember, we always are waiting for heparin for the ACT about two minutes, so it's about the same. And I think that's such a huge point. You know, we're kind of early in this transition to doing it, and a lot of the questions that came out early in the system was, how is the ER going to do this? You know, they don't even like bolusing heparin, how are you going to start a drip? And then the question about availability in the cath lab, it's a very practical tool to use if you're starting it there once you've seen the angiogram. In a way, and one last comment is that one of the nice things about Kangler, in my opinion, just my personal opinion, is that it pulls everything back to the cath lab, in that our field moved towards the ER has to do some part of the care, we do some part of the care, CCU has to do some part of the care, but the critical part that's important to us, vessel patency and lacus tenth thrombosis and clinical outcomes, we can control a lot of that in the cath lab, and all of a sudden we have an agent that we can control in the cath lab, turn on, keep it running, not much to do in the CCU, just have to reload the medication, which we can do in the cath lab as well. So it allows, from a practical standpoint, you know, we're all control freaks, maybe, some of us are, certainly I am, it's allowed us to bring it back into the cath lab and have that control. Yeah, it's sort of along the lines of I never give, I always give my own heparin, I don't have the nurses give heparin, so it's sort of the same thing. You're even worse than me is what you're saying. Alright. Just two quick comments on the bridging to CABG, a lot of the challenges that we face, community hospital, no CT surgery backup, so it's usually a transfer, and then the duration and the cost, because usually the bag would last you for like two hours and quickly pharmacy is going to call you and say, hey, I'm running out of bags, and I don't have endless amount of canglor, so you have to do something here. So that's one of the challenges we face. And the other point I wanted to make, and I hope I'm not an outlier here, but the debate for upstream platelets giving for ACS, non-STEMI, and all that, I found it's still up in the air whether you, because a lot of what I do is I wait until I define anatomy and then decide of what I'm going to do, and I still, and maybe I'm a little bit with the CT surgeons on this front, that I don't have to just emergently give you anti-platelets before I go in and look, and you know, most of the time, once you look, you know, you're not on anything, so then what do you do when you look? You just do the case and give it to them? In my practice, once I look, basically, you're going to get a sense of the complexity and the odds that this is going to end up being a CABG or complications will happen, and that will kind of guide your decision in what phase in your CABG procedure you're going to give your anti-platelet therapy, and usually, yeah, this Ticagrelor 180 or Crust, or I'll do Plavix 600, and then in my, this is just for me, the phases of whether it's before wiring or once I do my balloon, or even sometimes once I deploy my SENT, and I'm like, okay, load them right now, and you get a sense of that based on how the case went and what the anatomy looks like and all that, you know? Thank you. Yeah, so let's address two of the comments. The first one was about bridging. I don't, you know, we don't routinely check platelet inhibition via functional assays, but in the consensus statement, there is a role, they say, you know, about in this particular setting where if you are trying to figure out, you know, timing of surgery very soon after PCI within three months, and you can't do the short, and you can't wait for short-depth therapy, that you can consider functional testing to decide when you want to, at that point, start some sort of a bridging therapy. So that's something that you can use so that you don't have Ticagrelor running, you know, five days and make the hospital broke from the whole thing, so whether or not they're preloaded. We routinely preload, so, you know, but who says that it's, you know, absorbed in the system by the time we're taking pictures and fixing, and many centers don't routinely preload. They wait for the anatomy, so that's perfectly reasonable. The only thing I would say in that setting is that you may want to consider Ticagrelor on that crush loading so that if you need something more potent and right away, such as Kangalor, it's a safer transition compared to the—just because we have data showing that a clopidogrel preload does not transition well with Kangalor. Yeah, so I was always worried, you know, I've been doing this for a long time, and when I do it your way, which is basically that I see the anatomy, it's a STEMI, I do the case, I get good TIMI 3 flow, they're on heparin, the ACT is good, but I know that heparin is going to wear off, and it probably will wear off before the Ticagrelor kicks in. So I know there's a window, and I always know that if you do enough of these, once or twice of that year, I'm going to have to run—turn the car around and come back to the hospital for that acute sternum thrombosis on the first EKG. So for me, this has allowed a bridge of that, and so I don't have to come back, and not just for me, but for the patient. And so it's given me some peace of mind there. It's a rare event, granted, but I think if you do a lot, I think we'll see that. So I want to move on. For a rare event, you're doing routinely? We're doing a routine STEMI Kangalor. That's impressive. That's not—wow. So we pretty much are doing routine, all STEMIs. We have thousands and thousands and thousands of patients in trials where—before Kangalor I know, I know. You know, the heparin versus— But I think I believe the data that the ones who do have stern thrombosis, they don't do well. I know they don't die as much in the hospital, but they don't do as well long term.

medications

cardiology procedures

thrombus burden

stent thrombosis

clinical outcomes data