What I want to say is we spent a lot of time talking about cardiogenic shock. People sometimes forget that a key part of revascularization is anti-platelet, anti-thrombin treatment, and it's essential that we get good results. So the key parts is we remember whether you have iatrogenic plaque rupture or you do PCI, you are starting this cascade, and this is platelet activation, amplification, and aggregation. And without adequate anti-platelet thing on board, our results are inadequate. And we're going to come back to that in a little bit. And this is a key role, and listen, P2Y12 inhibition has dramatically changed what we do. Really, from Plavix on, it's, and we sometimes take that for granted. But you know what, another really important part is when you look at PCI, and I can show you 20 studies, all of the bad events occur in the first four to six hours, over and over and over again. This happens to be impact two, but we're going to show you another one. Almost all of the bad ischemic events occur in the first six hours. So we've learned a lot in the last decade. We have a ton of anti-platelet and anti-coagulant. Our goal is to prevent ischemia, and in particular, stent thrombosis, and target vessel and non-target vessel in mind. And then the balance of that is to prevent bleeding. And both acute thrombotic events as well as acute bleeding events can really complicate PCI. And with cardiogenic shock and auto-hospital cardiac arrest, this is amplified because these patients are more at risk for acute thrombotic events, and they're more at risk for bleeding events. So it's very important that we actually think about that. And that balance, that net clinical benefit or harm, really makes a big impact in our overall outcomes. Now there's a ton of anti-platelets and receptors and things that we have available. We're going to make it simple, and we're going to talk about a couple of key things, first of all. But when you look at patients who have STEMI with cardiogenic shock and auto-hospital cardiac arrest, you have to realize that this is a special population. And if you look at every single time when you look at cardiogenic shock and auto-hospital cardiac arrest, they have less good outcomes. They're less likely to end up with TIMI 3 flow. And part of that is because we are negligent about doing adequate anti-platelet therapy. And the problem with the oral agents are you get—all of these things are well known. I'm not going to go through them. You get delayed bioavailability. In particular, it's exacerbated by morphine and fentanyl. It's worse with ventilation. Obviously these patients are—you can't give oral agents many times. They're ventilated. They have vomiting. They've given heavy sedation and therapeutic hypothermia. And all of that affects it. So if you're trying to do an acute PCI in the sickest patient, you have to think you may not have adequate anti-platelet on board. And this is a great—I think Duane Pintle did this first picture of—that's the picture of the plavix in the stomach not doing very much good. And this is just one example. This is what fentanyl does. And again, you could show 20 things. So this—all of the stuff I showed you on that slide is absolutely shown to be true over and over again. And this is actually a nature review that kind of goes through when you have STEMI, what should you do? Number one, aspirin and pretreatment with a P2Y12. And then the anticoagulation, the debate about heparin versus bivalutin, I'm not going to get into that. But that we should consider keyenglur and the P2Y12 in native—naive patients and 2B3 inhibitors for bailout. One brief thing about 2B3 inhibitors, I'll say the problem with 2B3 inhibitors in this situation is bleeding. And cardiogenic shock and out-of-hospital cardiac arrest have the highest bleeding things and over and over again, that's exacerbated. So I think for us in terms of putting in a standardized protocol, and when you have a standardized shock protocol and out-of-hospital cardiac arrest protocol, you should be having the antiplatelet, antithrombin protocolized. It should be part of it. And so—and we're going to talk about that a little bit. What about pretreatment? Overall, for STEMI, people know that I'm a strong believer that you should have pretreatment. The benefits are—and it's a little hard to prove in terms of the timing from the randomized clinical trials. But there is substantial benefit that says the earlier that you get a P2Y12 inhibitor on board in combination with aspirin, the better you do in terms of TIMI flow, both prior to the procedure and at the end of procedure. And there's a decrease in stent thrombosis, decrease in ischemic events, decreased need for bailout 2b3 inhibitor. There's—disadvantages would be a little risk of bleeding, procedural bleeding, but mostly in patients who don't get PCI. And so when you talk about pretreatment, just a really important point, non-STEMI, you have about 10% to 15% of patients who get CABG, whereas in STEMI, it's only about 1%. So just as a general rule for this, with STEMI, absolutely you should put pretreatment into your standardized protocols. Whether it's prostaglandin, ticagrelor, or Plavix, I think most people use ticagrelor just because there's no black spot warning and because it works a little faster. So I think in most STEMI networks in the United States, how many use ticagrelor? How many use something else? So most use ticagrelor for sure. But for non-STEMI, you actually wait, and I think most people, non-treatments, pretreatment is not recommended. So what about onset? So this is an example in STEMI in patients with cardiogenic shock. Look at the delay to onset when you have with Plavix. Okay, clearly you have a significant delay, and more important, in unstable patients. This is Prasugrel and ticagrelor, and if you look at one hour, there's no intraprocedural effect at all in STEMI. Really none at all. And so you're not really getting peak effect with Prasugrel and ticagrelor until six hours post. So why do you think most of the events occur in the first six hours? Inadequate antiplatelet. It's completely what it is. And this is actually the opposite, ticagrelor, you know, again, I always say this, if ticagrelor was free, we would use it in everyone, because for a P2Y12 inhibition, it's immediate on, and you have really complete inhibition of ADEP-induced platelet activity. And then when you turn it off, you have about 30 minutes or so, 60 minutes for sure by the time it's back. So it's really perfect. You just turn it on, immediate antiplatelet effect. And this is the CANTIC trial design. So people said, what about crushed ticagrelor versus cangrelor? So this was crushed ticagrelor plus placebo IV versus crushed ticagrelor plus cangrelor. And this is what you see, and if you look at those two curves, so the blue is the placebo just crushed ticagrelor, and you can see not until one hour post do you end up with the same antiplatelet effect. So again, it doesn't matter, and the difference is with cangrelor, you have full antiplatelet inhibition. So I think it's worth knowing that. This was the, this is the CHAMPION-PHOENIX trial. It was a placebo-controlled trial. Everybody, it was a placebo bolus of cangrelor versus Plavix. Plavix is what the FDA recommended at the time with either a $300 or $600 bolus. Primary endpoint was a 22% reduction in the primary composite endpoint of death, MI, ischemic germ and revascularization, or stent thrombosis. Stent thrombosis, there was a 38% reduction. So this is why cangrelor was approved, and these are the events. Remember I showed you in time? The events are all in the first four to six, certainly within the first eight hours. And again, every acute Corning syndrome trial shows the same thing. So I think I'll end with this really. When you have STEMI, cardiogenic shock, auto-hospital cardiac arrest, all of these things serve to actually delay your oral antiplatelet. And we need to strongly consider whether this is the first place where you should actually have IV antiplatelet things. And two choices would be to use cangrelor, P2I12, versus use 2b3 inhibitor. And I think just the bleeding pushes this, and that early on, the rapid onset and the rapid offset with cangrelor, I think, puts you in that thing. This is actually a landmark from Phoenix that shows significant differences in the first two hours. After that, the differences are really small, and the event rates are really small. So the last one, and then I'm going to turn it over to Dr. Reimer. In particular, cardiogenic shock and auto-hospital cardiac arrest is very limited. There's really no randomized data. And they have worse challenges because they have worse STEMI flow at the end. So we talk a lot about mechanical circulatory support. We don't talk enough about adequate antiplatelet there. And the oral challenges are even higher than it is with just STEMI with these two patient populations. And I think there's a strong theoretical advantage for cangrelor. So we have put it in our standardized protocol for cardiogenic shock and auto-hospital cardiac arrest. And there's some good little data out there, but I think Jennifer's going to do that. So we're going to skip the discussion because we are waiting for lunch. And I'm going to just move into you're going to talk about antiplatelet therapy for cardiogenic shock and auto-hospital cardiac arrest.

anti-platelet treatment

anti-thrombin treatment

revascularization procedures

cardiogenic shock

ischemic events