So, my topic today is managing antithrombotic therapy. I'm going to go through the more recent guidelines that were published around this. There's not, like we've alluded to, there's not great randomized control data looking at larger lesions or EMR, but we'll talk about what data is out there and what the guidelines recommend and obviously how to extrapolate that to larger lesions. So, the objectives of the talk today, we're going to review antiplatelet therapy. I'm going to briefly review the mechanisms of antiplatelets and then get into the data around immediate and delayed postpolypectomy bleeding. Do the same thing for anticoagulant therapy. Again, review some mechanisms, go over data around postpolypectomy bleeding, and then talk about an interesting study looking at how to manage DOACs in the periprocedural setting. And then we'll finish off the talk briefly reviewing reversal therapy. So, again, I'm sure most of you are aware, but earlier this year, the ACG, in conjunction with the Canadian Association of Gastroenterology, published clinical practice guidelines on how to manage both antiplatelets and anticoagulants for acute GI bleeding and around the periendoscopic period. So, it's a great resource to refer to, but just as a note, a lot of these recommendations are conditional with very weak level of evidence. I'll allude to what recommendations there are as we go through the talk today. Anytime we're thinking about how to manage antithrombotics, as you all know, you should be thinking about what is the bleeding risk of this procedure. So this is a table that's outlined in the guidelines. For today's talk, the most relevant procedures are polypectomy and EMR ESD. So they've categorized procedures into either low-moderate risk, so that confers a less than 2% 30-day postprocedure bleeding risk, and then high-risk bleeding procedures, so greater than or equal to 2%. And so you can see our smaller polypectomies, less than one centimeter, fall into that low-moderate risk, and then our larger polypectomies, greater than or equal to one centimeter, and our EMR ESDs are kind of as expected in that higher-risk bleeding group. All right. So let's dip into antiplatelet mechanisms. I knew this was going to be a little bit of an intimidating slide. It's not my intention to go back to medical school, and those of you who know me know that I cannot review the basic science mechanisms of all this. But I do think it's fair to say that we manage these medications pretty often, and I, for one, do forget these mechanisms. So I wanted to take a quick second just to refresh everyone's memory on how platelets work. So anytime there's any injury to the endothelium, factors like collagen, von Willebrand factor, they get exposed, and they go to the platelet surface, activate platelets. Platelets like to activate each other. There's a very big positive feedback loop with these cells. So once a platelet gets activated, it itself releases factors like thromboxine, ADP, which then in turn go back to other platelet surface receptors and further activate platelets. The final pathway in this is the GP2B3A inhibitor. I practice that a lot, and I just crushed it. That then ends up activating fibrinogen and allows for platelet adhesion and aggregation and thrombus formation. And so that's how platelets normally work. So how do our antiplatelets work? Well, our more common agents are aspirin and then our P2Y12 antagonists. So aspirin, as you guys recall, is a COX-1 inhibitor. So that inhibits the production of thromboxine. That breaks that positive feedback loop that I just described. And then our P2Y12 antagonists are our agents like clopidogrel or Plavix, cangrelor, ticagrelor, prasegrel. And that inhibits the binding of ADP to the P2Y12 receptor. All right. So let's dive into aspirin. So before I get started, I just want to show of hands how many people tell their patients that they should stop their aspirin before any elective endoscopy? All right. So that's fallen, obviously, out of flavor to continue or to stop your aspirin therapy. And I want to go a little bit into why that is. So oftentimes, you know, your mind might go to, well, aspirin doesn't confer a higher bleeding risk, and that's not true. And so I'm going to review that data for you guys. If you look at overall post-polypectomy bleeding risk, this was a meta-analysis that was published from earlier this year that actually shows that there's an increased odds ratio in aspirin users compared to non-users when it comes to overall bleeding risk for post-polypectomy. So you can see there's almost a twofold risk for our patients that are on aspirin. When they broke that down into immediate and delayed post-polypectomy bleeding risk, they actually found that though there was an increased odds ratio, that didn't meet statistical significance. Looking at the paper, that's likely because the sample size dropped. But it's just important to know that overall risk is higher than baseline, and there might be a sort of trend toward significance or a similar effect size with an increased bleeding risk in both the immediate and delayed post-polypectomy bleeding risk groups. So why do we actually tell patients to continue it? Why don't we tell them to stop if there is an increased risk of bleeding? Well, that all goes down to cardiovascular events and the risk of cardiovascular events if you were to stop your aspirin. So this was a paper that was published in 2016 that looked at patients that came in with lower GI bleeding. And they looked at patients that were on aspirin and patients that were not on aspirin. And as you can expect, patients that were on aspirin had a significantly higher risk of recurrent lower GI bleeding. That makes sense. We've proven that overall bleeding is higher in our aspirin group. When they looked at cardiovascular events, they found that patients that continued their aspirin through their bleeding event had a significantly lower risk of cardiovascular events and a significantly lower risk of death from all causes. A very significant difference. It's important to note that in this study, over 90% of the patients were on aspirin therapy for secondary prevention. So that means patients that have established cardiovascular disease or are considered high risk. And not necessarily for us to know, but that's an ASCVD risk score of greater than 20%. So think about what the cardiovascular risk is in our patients when we're thinking about why they're on aspirin therapy. So the take home point for aspirin therapy and how to manage that for essentially all of our elective procedures is understand that there is an increased risk of bleeding when you're on aspirin therapy. But the reason that we don't stop it and the reason that the ACG and CAG recommended this is that when aspirin is used for secondary prevention, because of the risk of holding aspirin in cardiovascular events and death from other causes, the recommendation is not to hold aspirin therapy. Now, what does that mean for patients that are on aspirin just because they hear in the news that it's good for their heart, they don't have any cardiovascular disease, that they're on this for primary prevention? Well, in the cardiac literature, there are papers that say that almost 30% of patients may be using aspirin inappropriately. So using it for primary prevention, they probably don't need to be on it. So certainly not our purview to stop their aspirin. But I would say encourage a discussion with their primary care provider, with their cardiologist. Hey, do you really need to be on this aspirin therapy if you don't meet any of those high risk criteria, cardiovascular high risk criteria? Because our endoscopy may introduce a higher bleeding risk. So at least talk about interrupting the aspirin therapy for primary prevention, potentially holding it all together. And then finally, in our patients that are on aspirin therapy, the recommendation is to resume the aspirin once you feel like you've achieved endoscopic hemostasis. All right, so let's talk about our other antiplatelet agents. So first, I'm going to talk about clopidogrel and the overall bleeding risk with this. So this was a slightly older paper in 2013 that was, again, a meta-analysis looking at overall bleeding risk in our patients that were on clopidogrel therapy. And they found an over two and a half fold increased risk of overall bleeding in these patients after polypectomy specifically. When they broke this down into immediate and delayed bleeding, they did see that there was an increased risk of immediate bleeding. But again, that did not meet statistical significance. But when they looked at delayed bleeding risk, there was an almost five fold increase in delayed post-polypectomy bleeding risk in patients that continued clopidogrel. So again, pretty significant. This was a randomized control trial that was published out of Hong Kong in gastroenterology back in 2019. And this was a study that actually double-blind. It was a double-blind randomized control trial. They actually had patients come in for elective colonoscopy with polypectomy and had patients either continue their clopidogrel through the endoscopy or they put them on a placebo pill. All these patients resumed their clopidogrel the day after their colonoscopy. And they looked at immediate bleeding risk, delayed bleeding risk, and then overall risk of cardiovascular events. And as you guys recall, I just demonstrated that prior studies have shown us a five fold increase in delayed post-polypectomy bleeding risk on clopidogrel. But interestingly, this study actually found that there was no difference in immediate bleeding, delayed bleeding, or in adverse cardiovascular events between either of the groups. Kind of sounds a little bit weird. And if you look back, the authors actually kind of query, if you look at the baseline risk of delayed post-polypectomy bleeding in the placebo group, it's a little bit higher than what has been described. And so they actually posit that maybe this was because there was actually a higher use of electrocautery or hot snare polypectomy in the study, even for smaller polyps. So over 90% of the polyps in the study was less than one centimeter in size, but over 60% of the polypectomy technique was using electrocautery. So they say maybe they sort of kind of cover that effect a little bit because of the technique. What happens when we add other P2Y12 inhibitors to the equation? As you can see here, once you add other agents outside of just clopidogrel, you actually preserve what we initially found, which is that there is an increased risk in delayed bleeding. And that is, again, almost five-fold and greater than five-fold in this study. There are indications where you're going to hold antiplatelet therapy in patients that are higher risk. And so I just wanted to refer, there's a lot of great tables for reference that have been published in the guidelines. This just outlines how long you want to think about holding antiplatelet therapy based on the drug's half-life and then whether or not it's reversible or a reversible agent. All right. So what do we take away with our P2Y12 inhibitors, including clopidogrel? Remember that there is an increase in early post-polypectomy bleeding that didn't meet statistical significance but may be clinically very relevant. There is a significant five-fold increase in delayed post-polypectomy bleeding with all of these agents. And so because of that, the ACG and CAG recommend holding your P2Y12 inhibitor in patients that are on dual antiplatelet therapy. So you already have cardioprotection from that aspirin therapy. You do not need to increase that major bleeding risk by continuing the P2Y12 inhibitor as well. Hold the P2Y12 inhibitor. But then the question becomes, what about those patients that are not on aspirin that are on P2Y12 inhibitor monotherapy? For all elective endoscopy, they were not able to reach a consensus. Again, our conference this weekend is advanced lesions. Again, I think it's a little bit of a balance between why are they on that antiplatelet agent and then what is the bleeding risk of the procedure that you're about to undergo and having that discussion with the patient and their cardiologist. You want to avoid cessation in high-risk patients, avoiding cessation of dual antiplatelet altogether. And those high-risk patients, as you guys likely know, are patients with an MI or a stroke in the last three months or a drug-eluting stent in the last six months. Bare metal stents have largely fallen out of flavor, but this is something to remember. And then in terms of when to resume our antiplatelet therapy, they actually did not reach a consensus on when to resume it. Again, I think a lot of this depends and can be extrapolated on the data behind aspirin therapy. But it kind of depends on how confident you feel that you've reached endoscopic hemostasis or the risk of the resection bed for larger EMRs. All right. Another busy slide. I'm going to transition to anticoagulation therapy. I have prepped this talk, and you could still quiz me on the clotting cascade, and I probably can't outline it well for you. And my intention is not to review this again in its entirety, but I just want you guys to know that or remember that there are two pathways in the anticoagulation or the clotting cascade, the intrinsic pathway and the extrinsic pathway. And our anticoagulant agents work on several factors in both pathways. So our traditional vitamin K antagonists like warfarin work on multiple factors in both pathways. Heparin and low molecular weight heparin work on factors in the intrinsic pathway. Our factor Xa inhibitors are very aptly named because they inhibit factor Xa. Those are our direct oral anticoagulants like rivaroxaban, apixaban, adoxaban. And then we have our direct thrombin inhibitors that inhibit factor IIa, and those are our agents like dabigatran. Ultimately, we're trying to inhibit the conversion of fibrinogen to fibrin and prevent a clot from forming. All right. So what's the data behind anticoagulation and postpolypectomy bleeding risk? I don't think it's any surprise that anticoagulants increase your risk of postpolypectomy bleeding. This was a retrospective cohort study looking at the risk of postpolypectomy bleeding overall in patients not on anticoagulation versus anticoagulation and the different types of anticoagulants and found that there was a significantly higher rate of postpolypectomy bleeding in patients on anticoagulation compared to controls. And notably, there was no difference in the rate of postpolypectomy bleeding depending on what anticoagulant you are. So they all were statistically similar in the increase. Despite the study that I just showed you, there are additional studies, and they're referred to in the most recent guidelines, that actually have demonstrated that if you continue warfarin, the risk of postpolypectomy bleeding is actually non-inferior to those patients where warfarin is interrupted. So continuation of warfarin is non-inferior in terms of bleeding risk. And so based on those studies, the ACG and CAG have actually recommended continuing warfarin for elective endoscopy. They do make a note that if patients are undergoing advanced procedures that this does no longer hold true, and I'll get to that in a second. But I want to make note, especially for this recommendation, that the studies that they allude to are very heterogeneous. If you take a deep dive in the studies, they actually look at a lot of cold snare polypectomies, small polypectomies, and then even upper GI endoscopy and just biopsies. And that's what's driven this recommendation. For advanced procedures, they do recommend that warfarin should be held five days beforehand because of the higher risk of bleeding with those procedures. All right, so if we're interrupting warfarin therapy, we're obviously thinking about bridging these patients. This was a study that was, this was another retrospective study that looked at heparin bridge therapy and the risk of bleeding compared to either just continuing anticoagulation or holding everything all together. And they found, if you look at the graph on the right, they found that discontinuing your anticoagulation and putting these patients on a heparin bridge therapy increases the risk of post polypectomy bleeding significantly compared to just continuing your anticoagulation alone. So we can conclude that heparin bridge led to higher rates of post polypectomy bleeding in patients on warfarin. This was a study that actually looked at all patients with atrial fibrillation, and they looked at, all right, if we bridge these patients and compare them to patients that are not bridged, what is their risk of arterial thromboembolism, because that's what we're trying to prevent, and then major bleeding. They found that there was actually no significant difference in the rate of arterial thromboembolism in patients that were bridged versus not bridged. But as expected, the risk of major bleeding in the patients that received heparin bridge therapy was significantly higher. So based on this, the ACG and CAG have recommended against the use of heparin bridge therapy for elective endoscopy. Now, that's obviously not a uniform statement for all patients, because there are patients that do need bridging, and those are hard indications. This is a table that goes through what those hard indications are. So there are patients that, regardless of that increased risk of bleeding with heparin bridge, you have to just kind of eat that risk, because the risk of them having a stroke or a thromboembolic event is just far too high. So briefly, going over this table, those are patients with mechanical heart valves, patients with atrial fibrillation with very high CHADS-2 scores or CHADS-2-VASC scores, and then patients that have had a very recent thromboembolic event or that have an underlying thrombophilia that makes them high risk for a recurrent event. Anytime we're making a decision to bridge some of these higher risk patients, you're obviously doing it in conjunction with cardiology or hematology. So just a review that's kind of a central theme of all of these decisions that I'm talking about today. And then let's briefly talk about direct oral anticoagulant therapy. The ACG and CAG recommend holding DOAC therapy for elective endoscopy. If you think about that first study that I showed you with anticoagulation, there is a higher risk of bleeding, and so that's what's driving this recommendation. You all know this, but DOAC therapy is the half-life of these agents is dependent on renal function, some more than others. There are tables that are easily accessible through the ASGE or through GIE guidelines looking at each agent, their creatinine clearance, and then when to hold these agents. I will say I have looked at this table and the other tables that have been published a million times because it feels like everyone is on some sort of DOAC therapy these days, and I can never remember. I'm always referring to these tables. I'm always having to recalculate a creatinine clearance. I'm always having to do this over again. And so there have actually been studies that have looked at, hey, can we try and simplify this? We don't have to be doing all these calculations every single time. Is there more of a strategy that we can use that's a little bit more uniform and maybe easier to remember for us proceduralists? So that was the PAWS study. This was an international study that actually looked at not only procedures but also surgeries, and they looked at patients that were on direct oral anticoagulant therapy. They broke down their study into procedures that were considered high-bleeding risk and low-bleeding risk. And they said, all right, patients that are undergoing a high-risk bleeding procedure, we're going to hold their DOAC therapy two days before. We're just going to standardize that. The one exception is Dabigatran. That's more renally clear than the other DOAC agents, so they did stratify that based on renal clearance, but they said for the other DOACs, we're just going to blindly say that we're going to hold it two days before if it's high-risk bleeding procedure, and we're going to hold it one day before if it's a lower-bleeding risk procedure. And then similarly, in the post-procedure setting, when it comes to resumption of these agents, in those higher-risk bleeding procedures, we're going to resume it on day two, post-procedure day two. And on those lower-risk procedures, we're going to resume it on post-procedure day one. Again, just uniform strategy. And they looked at risks of thromboembolic events, and they looked at risks of bleeding. And they actually saw that across the board, regardless of agent used, the risk of major bleeding was less than 2%, and the risk of arterial thromboembolism was less than 1%. And they felt like that was clinically important and significant, and that it meant that this strategy is something to consider moving forward. All right, so just to summarize our take-home points for anticoagulants, the ACG and CAG do recommend continuing Warfarin, like we talked about, prior to elective endoscopy. Remember that that's limited data. It's only applicable to small polypectomy. It's not something that we should extrapolate for advanced endoscopic procedures. Heparin bridging is associated with a higher risk of post-polypectomy bleeding, and the recommendation is to not heparin bridge patients that are undergoing elective endoscopy. That being said, we should all be familiar with the indications to bridge with heparin. And then most direct oral anticoagulants can be stopped safely one to two days prior to procedure, again, taking into account renal function and then the overall procedure risk for major bleeding, and then resumed again within 24 to 48 hours post-procedure. I'm going to just briefly go over reversal therapy and just jump to take-home points for this. For antiplatelets, as you all know, there aren't dedicated reversal agents. It's really just the question of whether or not you need to transfuse these patients' platelets, and the overall recommendation is not to do that, and that's because of two reasons, really. Patients are on antiplatelet therapy, presumably for a reason. If you're going to load them with a platelet transfusion, you're potentially going to put risk for a cardiovascular event or a stroke or a TIA, so they recommend against that, and then the risk of a transfusion reaction in these patients that already might be decompensating. So they actually recommend just hemodynamically stabilizing these patients and going towards endoscopic hemostasis. And then for anticoagulant therapy, the table on the right is just for you all to know there are reversal agents available for all of our anticoagulants. The ACG and CAG actually recommend against the use of FFP and vitamin K for warfarin reversal, and they haven't reached a consensus on whether or not to use the PCC. And then for direct oral anticoagulants, because these agents have such a short half-life, the recommendation is to not use a reversal agent for these patients, even if they're presenting with the GI bleed. The recommendation is really just to medically stabilize them with fluids, blood transfusions if needed, and then let the therapy wash away, again, because they probably have some sort of underlying thrombophilic process. All right, so that's the conclusion of my talk. I know I didn't talk specifically about large lesions. There isn't great data about that. I thought maybe kind of dumbing this down and kind of going down to the bare skeleton of how we should manage this for even smaller polypectomies allows us to extrapolate this. There's clearly no data, but we know that our procedures are higher risk procedures. And so always need to be cautious about our antithrombotic agents. I'm happy to take any comments or questions. Thank you. Yeah, I think that is a really hard one. Honestly, in my training and my, I guess, limited practice as an attending, it's really just what they're on an anticoagulant for, how high their risk of a thromboembolic event would be. And then oftentimes, I will reach out to whoever is driving their anticoagulation. I'm sure a lot of centers do this, but when you're looking at when to hold anticoagulation, if we're reaching out to their primary provider, I usually do ask when they think it would be safe to resume it. That's assuming that I'm doing everything I can to reduce the risk of any sort of post polypectomy bleeding. So do using all the therapies that we've used. Usually, I would say I would try and hold it for 48 hours if I can, 48 to 72 hours. But it just sort of depends on what they're taking it for. So taking these recommendations, when someone comes to a screening colonoscopy, you would have been telling me you would have Warfarin, and you're trying to take polyp, high-risk polyp, and call them back. Yeah, I would not, I would not resect an advanced polyp with Warfarin. Yeah, I agree. That's sort of why I spent a little bit more time kind of diving into the studies that drove that specific recommendation on Warfarin. It was the exact same thought. You can't, you know, oftentimes, I think in advanced endoscopy, you're getting a referral for a large polyp, so you're going in already knowing what you're dealing with. And you can spend that time in the pre-procedure setting, working with the cardiologist, working with the hematologist, working with the patient, going over some of those risks. But yeah, if you encounter a big polyp on a screening colonoscopy, and they've continued their Warfarin, you absolutely have to bring them back. I don't know if any of the faculty have any other thoughts on that. Yeah, I mean, I would say for my practice, at least, the risks change so much when all of a sudden you encounter that large polyp. So usually, when you're just consenting for screening colon, you're not talking about higher risk perforation and that standpoint bleeding. If they're on Warfarin, you probably talk with them a little bit about it. But I think going into it, that would be part of my pre-consent process of, you're on Warfarin, we know you're at a higher risk. If we run into a big polyp, I can't take it out. And we'll have to bring you back at a safer date once we figure out what we're going to do with it. Because it's not just, you know, it's both the pre, as you're saying, and it's the post-procedure care that you were kind of getting at. Those things need to be sorted out. And once you know the polyp, it's a lot easier to have those conversations. When you're going into screening colonoscopy, it's really hypothetical. How do you find that? In my experience, it's very difficult to spend time on that. But the question is, what's the downside of having them stop for five days as a blanket or as a straightforward recommendation? Is there any downside of that? I think it comes into, why are they on it? And presumably, if they're on warfarin with no... Well, if they have atrial fibrillation, their CHADS-2-VASc score is like seven. And they're coming in for screening colonoscopy, you ask them to hold their warfarin for five days, and you're the one patient that has a perfect prep and no polyps. You've interrupted their warfarin. It takes them a little while to get therapeutic again, right? Warfarin doesn't become therapeutic right away either. You're not bridging this patient because of the risk of bleeding. So you're putting them at risk for a thromboembolic event during that period of interruption, presumably for no increased risk of bleeding because you haven't done any sort of polypectomy. And the risk of finding a polyp is 1% to 2%. So in that scenario, you can still do the bridging. And you have a reason for doing the bridging, taking the high risk of bleeding, because they have that high cardiovascular risk. And so I was, I mean, I'm not convinced of the advantage of just stopping it for all patients and not having a bridge or telling them that, yeah, you are at risk and spending time to do the bridging. You know, that's why these things are very difficult, right? And I think at least at Northwestern, the majority of our screening colons are still done with conscious sedation. So that gives you another reason. If I go in, I see a big polyp, probably not taking out a big polyp on conscious sedation, right? You're going to bring them back anyway to get them in our, with MAC, you know, be able to get our, you know, cap or just a cap on, get sort of our EMR kind of prep ready. And so then you have that ability to have that discussion about anticoagulation at a later date. But I think I have found in the few patients that I've had to have a discussion like this with, they're actually more than, they're actually hesitant to hold their anticoagulation. You have to admit them for bridge therapy. So it becomes a little bit more logistically difficult if you're going in saying, I'm just going to bridge you and hold your warfarin on the off chance that I do find a larger polyp or something like that. So I think it is just kind of a risk-benefit ratio or a discussion with patients, their providers, and kind of taking into account their opinion as well. So my understanding that you guys do the screening with Merced and Venerable? We do, yeah. We still do a majority of our patients with conscious sedation. I'd say a lot of practices still. That's not unusual. I mean, with the social media, they come and ask for it. Yeah. And sometimes they don't get it. Yeah. Yeah. Can't give everyone what they want, Harsh. Nice man. All right.

antithrombotic therapy

recent guidelines

postpolypectomy bleeding risk

aspirin therapy

P2Y12 inhibitors

management of anticoagulants