All right, so I have the last talk of the section, which is hopefully going to wrap it all together with optimal antiplatelet strategies in high-risk patients, which I think we all know now is a hard question to answer. So I kind of separated this into two parts. One is now, and one is the future. And just talking about now, really to summarize what my co-panelists have said here, you know, the goals in using antiplatelet therapy in patients like this is we want rapid onset to optimize reperfusion. We want to avoid known issues with cardiogenic shock, with the two most prevalent being impaired gut absorption and impaired hepatic CYP metabolism. We also want rapid washout, or the ability to reverse the antiplatelet if urgent surgery is needed, usually like LVAD or transplantation in this patient population. And we want to minimize increases in bleeding, specifically within the subgroup that we often take care of, which is those on mechanical circulatory support. And we know that cangrelor is a great drug, and we know that it solves a lot of these problems, but I think we also have to acknowledge that there are some questions that are left to answer, which is, you know, is this safe on patients on mechanical circulatory support? How long should we continue it? And if we need another antiplatelet or an anticoagulant, which ones do we use in combination? And I've been fortunate, and thanks to the course directors for inviting me for a third time to give this talk this year, but in an effort to keep it fresh, I went through the data in the last year. I know this audience knows most of the major trials, so I selected the smaller trials that were just the newest, and there's not many, which is unsurprising, but there was one study that was published here in the last year that was a retrospective study of five years of data with PCI plus ECMO, 37 patients, and they got the variations of DAPT. Forty-four percent got clopidogrel, 38.9 percent got ticagrelor, 16.7 percent got paracegrel in the control group versus the experimental group was cangrelor. And what they found was no difference in bleeding. You can see that there was high bleeding rates in both, but no significant difference in bleeding and also no significant difference in thrombotic events. And the only other new trial that I could find that was published in the last year was this single center experience looking at those who got PCI on ECMO that used cangrelor plus bivalirudin, and they did not use aspirin, just cangrelor plus bivalirudin. And what they found was a pretty consistent thrombosis rate with what was seen in the other trials at 14 percent, and they found a bleeding rate of 21 percent. So still high, but a little bit lower than it was before. And I think one of the things we talk less about but is a real issue in those who manage these patients on a day-to-day basis is thrombocytopenia. And almost always when you have a patient on mechanical support, especially if it's ECMO plus impella when you're using two devices at the same time, you almost always run into thrombocytopenia at some point in the ICU. And the question always comes is, should the antiplatelet be stopped, and when should platelet be transfused, and is there a different threshold if someone's had a recent stent versus not? And we recently had an M&M at our institution, actually, where we had an intracranial hemorrhage for someone who was on anticoagulation with thrombocytopenia. And we went through the data and we said, what is actually the guideline-recommended platelet count that people should aim for on mechanical circulatory support? And I think that we all probably have a number in our head of 50, which is really extrapolated from oncologic literature and not from this patient population. But I pulled the ISHLT guidelines that were published in 2023. So they don't recommend a platelet count that's consistent throughout the course, but they say if the patient has severe bleeding, that we should aim for a platelet count of 100, which I think is higher than most of us would do. And if you look at the ELSO guidelines, which were a little bit outdated at this point, they were published in 2017, but they actually recommend a platelet count of 80,000 to prevent bleeding while on ECMO specifically. So I'd be interested to hear what other people's experiences at their institution, both my co-panelists and the audience. But in an effort to keep this practical and stimulate discussion, I'll tell you how we manage at Mount Sinai, which is all shock patients receive cangrelor. And if we do need anticoagulation, which we often do in conjunction, we prefer heparin to bivalorudin just for the ability to reverse. If the patient does develop thrombocytopenia, we do shoot for a platelet count of 80, and we do continue cangrelor along with platelet transfusions, although I don't know. I'll be interested to hear what others say. We don't continue anticoagulation at that point. If the patient is bleeding, we shoot for a platelet goal of 100, and we stop everything, both antiplatelet and anticoagulation. We don't necessarily want that to be for a short period of time, but we do. And we continue cangrelor until they're liberated from all inotropes, and we're totally sure that they don't need LVAD surgery or transplant. So just quickly on the future, there are a few things that are going to come out in the next few years that I think will change the way that we approach these patient populations. One is the reversal agent for ticagrelor, ventricimab, which is a monoclonal antibody that can reverse ticagrelor. It's been proven in preclinical studies and some early clinical studies that it does work, it does reverse ticagrelor, it does lead to sustained reversal of ticagrelor, and they just were accepted by the FDA to start hopefully looking more at this in early 2025. And then there's two new antiplatelets that are kind of on the up and coming. I might butcher the names of some of these, but salatogrel, this is a subcutaneously administered G2Y12, and this might be useful for someone who has limited IV access that we also need a potent rapid onset antiplatelet for, and there's currently trials undergoing for this drug. And then also zolinfaban, hopefully I got that one right, but there is a trial that's ongoing with this drug, which is another subcutaneously administered drug. This is a GP2B3A, and this is a drug that specifically is being looked at given on the way to the hospital by EMS for ST-elevation myocardial infarction, and hopefully we'll have some of this data soon and see how it could be used in this patient population. So in conclusion, I think that we just don't know optimal antiplatelet therapies in the high-risk patient population, but hopefully we'll have some new guidelines and new pharmacologic agents in the next few years that will help us to continue to optimize care for these patients.

antiplatelet strategies

high-risk patients

cangrelor

ticagrelor reversal

subcutaneous antiplatelets