specifically in relation to AMI and cardiogenic shock. I'm gonna do a whirlwind tour of, I think, recent data that we've published over the last couple of years for cangrelor in AMI CABG patients and in cardiogenic shock patients. I'm an interventional cardiologist at Duke. Here's my disclosures. Primary one, I'm principal investigator for a cangrelor registry called CAMEO that I'll talk about. So just to start off, I think the Sentinel trial for cangrelor was CHAMPION-PHOENIX. And again, this actually excluded patients with cardiogenic shock and cardiac arrest, but that's really where we started to find out information about cangrelor. So patients with elective or urgent PCIs were randomized to clopidogrel loading or cangrelor with a primary efficacy endpoint that includes all the ischemic risk we care about, urgent revasc. And you can see that cangrelor outperformed clopidogrel. And outperformed clopidogrel with results with regards to stent thrombosis without significant increase in bleeding as well. So I'm sort of setting the stage for where cangrelor came onto the market. Now there's been a lot of need for observational data. I think specifically within populations like AMI and cardiogenic shock, harder to sometimes sort of see what the real world experience is for those patients in a trial setting. So a registry is really ideal to sort of look at basic observational data. CAMEO registries now 5,000 patients in the U.S. from all the sites listed on the right. It's patients that had an acute myocardial infarction, either a STEMI or non-STEMI. We enriched the registry about two for every one patient got cangrelor for every one patient that got an oral P2Y12 inhibitor so that we could ask a lot of the questions that I'm going to describe here. So one of the interesting things, and I've certainly seen this at my institution, is the transition is oftentimes not the most eloquent transition. So we've all used cangrelor in the cath lab, two hours or for the duration of the procedure, and then made sure that patient had ticagrelor, taking it in the lab in front of us while the cangrelor's still running. We know it's okay to overlap. But what happens when that doesn't happen? Well what happens is when we looked at patients across the U.S., a median gap time of about two and a half hours. So two and a half hours, cangrelor's way out of the system. Remember, half-life's like three to four minutes. Way out of the system at that point, and then we're giving a clopidogrel load, lots of potential concerns for stent thrombosis in ischemic events. We also looked at the question, well what about those patients, you know, one of the things I commonly see, you see a STEMI patient down in the ER, they put ticagrelor, they give them ticagrelor, or plavix, or whatnot, and then they roll up, and you've got access, and you're already into the procedure 10 to 15 minutes later. Do we think that patient has adequate oral P2Y12 inhibition at that point, particularly if they're in shock, or the patient that's on chronic therapy at home, but you're not really sure if they're taking it adequately or not. So we looked at a subset of patients within the registry to say, all right, they got an oral P2Y12 inhibitor at some point, and then you gave them kangrelor during the case. Is that overlap of platelet inhibition, does that lead to increased bleeding? And one of the findings we found is, regardless if it's a higher potency oral P2Y12 inhibitor or clopidogrel, really no significant difference in bleeding if you got upstream, got kangrelor downstream, or just got oral upstream. So I think increasing confidence that if you feel like you need additional antiplatelet therapy during the PCI, during the case, okay to use kangrelor. But really the primary place I think that kangrelor is used currently in our current practice is either in cardiogenic shock or in CABG patients, and I'll talk about CABG here in a moment. And for all of the reasons that were outlined prior, kangrelor is ideal, right? Because these patients are coming up, poor gut perfusion, oftentimes they're vomiting, they're mechanically ventilated, they're on maybe an opiate for sedation purposes, and you really have unclear gut absorption of oral P2Y12 inhibitors. We've all seen that tweet by Mike Gibson where the plavix is sitting in the stomach and it's not going anywhere, and I think that sort of brings fear to people like me that my stent's gonna stay open subsequently. There's really little data about kangrelor in the real world. There was a small single center study published, 147 patients who had gotten kangrelor, and only about 26% with clinical cardiogenic shock. The early study showed that the bleeding risk, mild to moderate bleeding episodes, not extremely high. Now we know cardiogenic shock patients are more at risk for MACE events and bleeding, but at least showed that there was not extremely high bleeding when using kangrelor in cardiogenic shock. So we set out to look at this question in our cohort and cameo. So we had at that point 2,300 kangrelor-treated AMI patients about 240 who were in cardiogenic shock at presentation, median age of around 66 years, 36% had diabetes, about a quarter underwent multivessel PCI, and 60% had MCS support. Some had multiple types of MCS. About 20% needed thrombectomy, and 20% needed MCS for more than five days. You can see that about 50% had a thrombus visualized, but most had restoration of flow at the end of the case with TEMI-3 flow, as you can see. And so a couple things that we noted here. First off, the variability of kangrelor across cardiogenic shock is mostly variable about what site you're being treated at. So for most of us, you use kangrelor in your run-of-the-mill PCI for two hours or for the duration of the procedure. For patients in cardiogenic shock, you might expect it gets used longer, right? Because they may not have internal access, you may not be confident about their gut absorption. So about twice as long. We had patients going for days and days on kangrelor while mechanically ventilated. The IQR here was two to 21 and a half hours. And there was a big mixture. So some actually stayed on the PCI dose that entire time. Some went down to the bridge dose. And the single biggest factor of what happened was, again, what institution you were at. This was just published in the Journal of Cardiac Failure for the interventional edition. The kangrelor in cardiogenic shock, we had about 166 transition to Ticag or Prezegrel and about 40 to Clopidogrel. Maybe not surprising was that increasing age was associated with shorter infusions and MCS was associated with longer infusions. The MACE rates were about 42%, had some sort of in-hospital MACE events. 25% had a bleeding event. And these were among all the kangrelor-treated cardiogenic shock patients. So I think a sick population, relatively similar, I think, to some of the shock registry data and some of the data out of NCDR as well. One of the things we did know is that your risk of bleeding actually was higher if you got the bridge dose. And so I thought, well, why is that the case? It's a lower dose. But actually, those patients, by and large, got longer and longer infusions for various reasons. Sicker, mechanically ventilated, not doing well. Your risk of bleeding also increased for MCS utilization, large pore access, and if you're a diabetic. Quickly to move on to kangrelor and CABG and AMI. I think this is really fascinating, actually, the variability in how we use kangrelor to wash out oral Pty12 inhibitors prior to bypass surgery. So, Dominic Angiolillo published in JAMA in 2012, over 10 years ago, the BRIDGE trial. And that was really the first time that we had the concept of using BRIDGE dose kangrelor when a patient's got an oral Pty12 inhibitor, maybe needs to wash out over a period of time. Maybe it's had a recent PCI, but it's going to CABG. 210 patients with some upstream oral Pty12 inhibitor were randomized to either a BRIDGE dose kangrelor or to placebo prior to CABG. They were predominantly looking at the pharmacokinetics and dynamics, not necessarily outcomes here. But you can see in those patients that were on that BRIDGE dose kangrelor, the .75, the PRU significantly lower compared to placebo, but because of that nice, short half-life, go back to the placebo group just prior to CABG. So, again, I think it relays and relieves a lot of the concerns about bleeding associated with kangrelor prior to CABG. So then we wanted to say, well, what's our experience within CAMEO for bypass surgery? We had about 250 patients that underwent bypass after their index AMI, and about 42% of them were treated with kangrelor, and the patterns were all over the place. So 11% treated with an oral PCY12 inhibitor, presumably then got washed out, were on kangrelor, then went to CABG. 30% treated with kangrelor only. 21% treated with an oral PCY12 inhibitor only, then got washed out. And about 40% got neither. And I think one of the things I find most interesting is length of stay. So this is length of stay up to their bypass procedure. This doesn't even include the recovery from bypass to the end of the hospitalization. So from time from admission to CABG, if you got kangrelor only, your median stay was about 3.3 days. If you got any combination of oral therapies because of the washout periods of time, median length of stay going into CABG was about six days. And again, doesn't account for all of the recovery post-CABG, so about double the length of stay already just waiting for bypass surgery. And then the other thing that we looked at was the kangrelor dosing and duration of infusion. So about 64% got the PCI dose. So they got the PCI dose for the entire duration waiting for CABG. About 26% got the bridge dose only, and about 10% got somewhere in between. And this is, in some of these patients getting PCI dose, this was days and days. You can see the IQR for the median was up to 4.1 days. So days and days of a PCI dose waiting for CABG. And a couple of us, and this was a publication of a few of us at Duke, Alex Sullivan and Jack in 2021 to sort of look at what are some protocols we can put into place? So there's those patients, obviously, they come in. I had a patient just the other day, big RCA semi, shoot the left side. You gotta open up the right to stabilize them. Left side is left main bifurcation, diffuse LED, diffuse CERT. And you wanna get them a good lemagraft, potentially. So fix the RCA, put on cangrelor, then sit there and get bypass surgery for the rest of their disease. So there's a couple protocols out there, I think, to help aid in what we should be doing with these patients, specifically in the washout for the oral, when to start the cangrelor when you're doing the washout, and then when to stop it in relation to bypass to avoid bleeding. So overall, in conclusions, we've taken you through a whirlwind course of registry in AMI and cardiogenic shock. We have highly variable practices remain in the use of cangrelor to treat CABG patients, to treat cardiogenic shock patients. We know it can be effective and safe in treating AMI patients without adequate upstream platelet inhibition. I hope I showed you that. We know that it's frequently used in patients with cardiogenic shock because of gut malabsorption, because of concomitant opiate use and lack of enteral access. And we know that patients with cardiogenic shock being treated with longer infusions oftentimes are getting the bridge dose infusions, but as I showed, also PCI infusions, the higher dose infusion. And then again, for how you're treated prior to bypass surgery, really the greatest factor is what institution you're being treated at. So look forward to the rest of the presentations and a good discussion here at the end. Thanks so much.

cangrelor

acute myocardial infarction

cardiogenic shock

CAMEO registry

PCI procedures