Chapters Transcript Video Status Post PCI - DAPT Back to Symposium My talk is, uh, gonna be, uh, like Dennis said, uh, about DPT post PCI and. This is a really daunting topic. I could talk about some of the foundational trials, one or two of them, and, and spend double the amount of time. So what I'd really like to focus on today, and I think it'd be helpful is, you know, we can all read the guidelines and sort of read those flow sheets which we'll go over. Don't worry about that, um, but you know, I think it's, uh, it's helpful to dive into what's new and, and sort of some of the more complex clinical decision making that we run into and with DPT, uh, no disclosures. So, uh, uh, we'll go through this briefly, um, just, um, gonna start with some principles, uh, post-DAPT, um, and people post PCI, and, and really, I think we all know that the majority of events, uh, with contemporary stents occur in the first year post PCI. You know, really when you think about stent thrombosis, which, um, has a high mortality rate, you're worried about the 1st 1 to 3 months. So that is our sort of warning window there. Um, after, um, one year, there's still an incremental increase in stent thrombosis, but, you know, really it becomes more about, um, progressive atherosclerosis of the stent or, you know, uh, unrelated, um, to the stented vessel in question. So another coronary vessel, for example, you see on the right side here this is, uh, taken from, uh, one of the foundational trials, the ADAPTDES trial. And really, um, it's kind of hard to, to parse out, but, um, if you take my word for it, really what you're looking at is the risk or the rate of stent thrombosis, um, over time and you can see, um, really for all comers, but especially in people with ACS that that 1st 11 month if you didn't believe me, is, uh, is really the risk, uh, factor that we're looking at or the, the zone of risk, um. And of course it's higher in ACS than stable coronary disease. So, um, this is taken from the most recent, uh, guidelines, um, sort of, uh, an update for ACS, and I think we know a lot of this, but, you know, really, um, the standard of therapy for years now has been dual antiplatelet therapy after ACS, um, you know, whether that be STEMI, um, in STEMI, um, or unstable angina. Um, it's usually gonna be aspirin and then some sort of PTY-12. Um, you know, the guidelines will tell you now, essentially, um, there's preference for tagrolor and Prasagrel. You know, there is a, a, a role in some cases potentially for clopidogrel. Um, you know, the, the problem there is we'll get to later, is that, uh, it may not necessarily be wrong for the patient, but you don't really know if that's the right patient, uh, for that drug. And really, you think about people that may have some genetic mutations, you know, maybe 20% of the population. So, um, you know, if you don't know that, then you don't know if you're putting patients, uh, on the right therapy there. Now some studies have compared people that they know or do not have those genetic mutations that make clopidogrel less successful. Those people can do almost as well or or essentially as well as ticagrelor or Prasagrel, but right now in our guidelines we're gonna say Tyagrelor Prasagrel first, um. And, um, you know, over there on the right side, just another thing to mention is that anyone who has a history of a stroke, um, or TIA, uh, you wanna avoid Prasagrel, but otherwise, um, you know, Press grill, uh, Te Aguilor, I, I think I favor Tecaguilor, uh, you know, kind of up front in a lot of patients, but Press Girl is really nice once a day. So that's, uh, just a, a little bit of background there. And then, uh, this is a comparison of our old guidelines com you know, with the new 2025 guidelines. Um, you know, there are some similarities there, um, but, you know, I think that, you know, what we'll really focus on is that again what I said earlier, ACS, you're looking at tagrolo or Prasagrel that are favored, uh, they've been shown to reduce stent thrombosis and, uh, reduce mace. Um, and we're gonna kind of get into this, this whole crux of, uh, those two medications specifically are gonna reduce stent thrombosis, reduce mace, uh, but when can we discontinue them? You know, they're obviously more potent and they can increase the risk of bleeding. So we're gonna be talking about that constant interplay between, uh, you know, when do I need to have that really intense medication, when can I discontinue it, um, after that sort of, um, you know, danger zone or that time period that I mentioned earlier, um. So, uh, just some other things to mention and, and this is what I'm gonna go into later, and I think that, um, you know, it's something where, you know, on a day to day basis you may not think about it quite as much, um, but so in patients who have tolerated this is in 2025 guidelines, patients who have tolerated, um, DPT with Tyagrelor, uh, the recommendation is that, um, after one month if they have had no problems you can transition them to Tharoor monotherapy. And that has been, uh, and I'll, and I'll prove it to you, has been shown to reduce bleeding and, uh, and helpful overall in patients, um, you know, the other things, uh, to get into here are, of course, um, you know, talk to cardiology maybe, uh, a, a good bit about when can this patient stop their medications if they're gonna go for surgery, um, you know, that's really unchanged. You're looking at 3 months for stable, um, ischemic, uh, heart disease and then ACS 6 months roughly. We'll get into all the, the, the nitty gritty details of that, but then also, as we'll come to later, um, there's the thought about switching de-escalation of, of, uh, of P2Y12 or an antiplatelet in general, and we'll talk about some of the strategies for that why some might be more helpful than the other, but, um, you know, the my general. Takeaway would be here is that you know the old things are old, you know, there's still gonna be preference for 1 year of DAPT post ACS still gonna be 6 months for DAPT roughly after, um, you know, for someone who got a PCI with stable heart disease, uh, stable ischemic heart disease I should say. But the, the big things to take away are, you know, think about tagguilor monotherapy after one month, which is short dap, uh, think about early transition, um, to, you know, de-escalate patients that may be, um, on, on dapt with Tyagguilor or Prasagrel, de-escalating them possibly to clopidogrel, and then think about shorter therapies in general. Um, the last thing that, that I wanna get to, and it's probably the, the newest thing, you know, short ddapt is on everyone's minds, of course, but then, um, I'm also gonna talk about extended, uh, mono, uh, antiplatelet monotherapy, which is something that's really, I, I think impacted me, uh, and my patients, uh, in the clinic recently, I should say. Um, I've gone through a lot of this. We talked about de-escalation. So, um, again, so many studies, and we won't go, uh, into all of them, of course, um, have shown the feasibility of withdrawing, um, P2Y12 inhibitors early, um, a lot of those, um, you know, involve clopidogrel, um, oftentimes they, uh, enroll patients that were lower risk, and, um, a lot of times those studies may have been underpowered for ischemic events. And as we talked about, short duration DAP, that is 1 to 3 months of DAPT followed by some sort of uh P2Y12 monotherapy has been shown to reduce bleeding, uh, without any, you know, sort of increases in ischemic risk. So you don't really have to, to make that, you know, terrible decision necessarily in some of these cases that I'll show, and that's compared to, you know, our standard 12 month of DAPT and, and I think it's really important because I see a lot of patients and, and I sort of will do it myself, you know, that clinical inertia you have a patient who. You know, maybe it's, uh, 14 months out from their, their PCI, their ACS, um, there's a lot of clinical inertia to continue DAPT, but I think, uh, as we're gonna see that that is not free, that comes with a pretty significant increased risk of bleeding, and some of these new strategies will, will sort of, you know, they will help your patients, and I, and I think they're interesting to think of, to talk about. And again we, um, are gonna go into the, the more of the details of the studies, but. The, um, the tagrular monotherapy really is the only short dap that's shown, um, uh, reduction in ischemic events. So, um, we'll get into that a little bit more. Um, you know, what is the optimal duration of DAPT? So just, um, you know, something that we've already mentioned here and, and we probably know, but, you know, extended DAPT, uh, greater than one year after stenting versus aspirin monotherapy, it reduces the risk of MCE. So you're thinning the blood, you're protecting that patient after a stent, but it comes at the cost of higher bleeding. So that's the tug. Um, you know, the, this study here, uh, you know, uh, DAP trials, um, the interesting thing to think, you know, to look back on them, you know, you get DAP scores and, and drive those things from these studies, um, to think back though, it wasn't all that long ago, but, um, and over this, um, excuse me, in this trial, for example, over half of the. Patients, um, had out of date stents. So, you know, with newer, um, with newer generation drug eluting stents, um, you know, the risk of stent thrombosis is much lower. Also, you know, and, and also we won't really get into the trials of that, but using intra coronary imaging, intravascular imaging has also improved outcomes as well. And, and again, just to, um, to kind of hone in on that a little bit, if, if you, there's been some subgroup analysis of these sort of landmark trials and when you look at more contemporary drug eluting stents, there's no real ischemic benefit from the, uh, extended adapt. So you're getting that bleeding risk, not much, uh, or if any ischemic benefit. So, uh, this is just a really nice slide. I thought it's a, um, meta-analysis of about 35,000 patients, uh, from JAC, and it showed, um, just this benefit of short versus prolonged dapt and, you know, this was in the range of 1 to 3 months. Uh, here we don't really necessarily break it out by ACS or stable coronary disease. They sort of lump them all together. Um, but you see here that, um, for, you know, for a lot of different things, you get a trend towards shorter adapt on your left, I suppose. Um, but, um, overall, uh, death is, is, death is less with short dapt, more, uh, more adapt, more depth, extended dap, I should say. And we're gonna talk about DAP de-escalation. I there are a lot of ways you could parse this out, but, um, I'm gonna talk about aspirin discontinuation is a form of DAP escalation. This is within 1 year or within 6 months of, uh, PCI. We're gonna talk about ways to switch P2Y12 inhibitors and the data behind it, and then we're gonna talk about, uh, potential P2I12 inhibitor discontinuation. So for aspirin discontinuation first, so this really gets into, um, you know, there's all these trials that come out of short dapt, you know, what is, uh, what's the newest data, what's the consensus, and, and really, um, if you think about withdrawing aspirin and some sort of P2F12 monotherapy, think about Plavix for, or excuse me, clopidogrel first. So overall, there is a trend that, that clopidogrel is probably OK, especially within. The 1st 6 months after ACS, for example, but there have been, you know, a couple trials, including, um, an Asian trial that showed that, um, clopidogrel monotherapy after ACS increased the risk of death potentially, you know, there may be an issue there where, um, the individual response to clopidogrel is different because of, um, um, the alleles, uh, uh, abnormal allele response I should say. Um, but we don't know, is it because of, is that patient population not responding well to them, or is it just that a lot of these, uh, you know, the studies that have shown not so nice of a benefit with clopidogrel, um, maybe they're within that 1 to 2 month window where you need a more potent P2Y12. The safety of Prasquiro monotherapy, you know, withdrawing aspirin, continue, uh, continuing Prasquiro monotherapy after a short dap hasn't been reliably proven as well, you know, uh, my asterisk there is there was a Japanese study that looked at a low dose Prasagrel, I think 3.25 mg, something like that, uh, very early, uh, uh, after a month after ACS that didn't show benefit, um, so, you know, it'd be interesting to see what comes out in terms of, um, more, you know, studies that are structured with higher, uh, more reliable doses of Prasagrel, but. Uh, ticagrular monotherapy that has really robust evidence and that's why it's made it's all way all the way to the guidelines and I think it's interesting, you know, sort of why, why is this the case, um, and really there's, uh, been some experimental models that show that. Um, aspirin, uh, really just provides limited platelet, uh, excuse me, excuse me, uh, limited additional platelet inhibition in healthy people that are on potent P2I12 inhibitors. So, uh, the P2I12 inhibitor, you know, it, it, uh, can also interfere with, uh, thromboxane A2 induced ATP release. So maybe you're getting a lot of bang for your buck just with the P2I12s. So I'll just zip through these just to, to kind of prove it to you. Um, this was a sort of, these are gonna be pivotal trials initially that approved how effective short DAPT is with TAguilar. And so the, really the foundational trials, the Twilight trial, these were high-risk bleeding and ischemia patients who underwent PCI. Um, they tolerated DAP for 3 months and then they were stratified to continue DAPT or Thaguilar monotherapy. And those patients who underwent PCI and had tagrolo monotherapy, um, they had a lower incidence, incident of bleeding and then no difference in MACE compared to people who were on standard APT. These are again, high risk bleeding and ischemia patients. Uh, there's been several sub-studies of, of the twilight trials. There's twilight ACS that showed the same thing. Again, these, um, the initial twilight trial, interesting is they include ACS and stable coronary disease patients. This was, uh, you know, solely ACS patients. And then finally on the right side, you see, um, a substudy twilight complex. So these are really complex coronary, um, interventions and the same outcome was shown as well, um. So my transition, uh, predictably didn't work very well here. So, um, you'll just have to, uh, trust me that, you know, what I want to talk about is there's a couple of different trials too that prove the same thing. So, um, you see, um, behind it to the, uh, right there's the SmartChoice trial and then in the, in the foreground, that's the Smart Choice two trial, excuse me, and, uh, both of those studies essentially have shown that, um, that, that. Antiplatelet monotherapy with Tharoor, uh, P2Y12 has, uh, uh, increased, um, or excuse me, has shown no really difference in mace just like the other trials, but is, uh, trended towards a less risk of bleeding. Um, the Tico trial as well as the other one hiding behind there, you know, the other interesting trial just to mention Global Global Leaders trial, this is a little, um, you know, not the way we do it. So the, the setup here is a little strange, but, um, I think it's a very important study. Uh, this, uh, study looked at Tyagor plus aspirin for 1 month, then they switched those people to Tyagrular monotherapy for 23 more months versus, um, standard apt with either aspirin, Plavix, or aspirin, Tyagrular for 12 months. And that study showed that 1 month of DAP was not superior to standard AAPT for mortality at 2 years, no difference in stent thrombosis, MI, uh, or bleeding, and, uh, tagrolo monotherapy was associated with fewer ischemic events overall though, and numerically increased serious bleeding events in that trial. The next thing just to mention, uh, also kind of going down now, we're looking at trials that are one month of DAPT. So, uh, stop dap 2 and then stop dap, uh, 2 ACS, and then there is a, a combined, you know, cohort study but of stop dap 2. these studies have, um, you know, been looking also at monotherapy after ACS or stable coronary disease. Stopdap 2 was a mix of those two. Um, after 1 or 2 months of DPT, clopidogrel monotherapy was superior in the bleeding outcome and non-inferior in the cardiovascular outcome versus still 12 months of standard AAT with aspirin and Plavix. So, um, you know, some, uh, some acknowledgement that Plavix might be worthwhile there. Also stopped at 2 ACS, essentially showed the same thing, but in ACS patients, and that is the, you know, that powerful group that we're talking about. So when I said mixed, uh, results with clopidogrel, that's what I meant. Very important trial, um, also kind of supporting the one month of Tyagoror is the ultimate DAP trial. Uh, this trial, uh, essentially stratified people after 30 days of standard AAPT, uh, Tyagorlar monotherapy or standard AAPT, and, um, also, um, had really good findings, reduced risk of overall bleeding with no different inmates. Um, and then finally, um, TPASS, um, another trial, uh, also I think is very important just to mention is that this was less than one month of DAP. So, um, less than one month of DAPT, um, resulted in, uh, less major bleeding overall, um, but actually there was, um, uh, superior for MC which was driven probably by that less bleeding. So that was, uh, a very interesting study and really, I think, uh, all these trials plus many more that I didn't mention support the taggular monotherapy. Um, just a couple, um, you know, uh, meta-analysis to mention, uh, that sort of support that idea. Um, this is a, a very large meta-analysis that showed that after aspirin was stopped a few months, 1 to 3 months after PCI and people were transitioned to P2Y12 monotherapy versus traditional adapt, uh, bleeding outcomes improved, no difference in MCE. So just kind of proving our point here again. Um, again, recently, a big meta-analysis at Sky, uh, in, uh, this year, excuse me, showed that after 1 to 3 months of, uh, DPT, uh, tharular monotherapy, um, was, uh, was significantly, uh, important to reduce all calls mortality, a 51% reduction in major bleeding, which is huge, and then a moderate reduction in mace. Um, You know, next, uh, just to, to kind of move along that same trend, when you switch P2I-12 inhibitors, this is the Talos MI trial. Uh, really here we're thinking about, you know, what are you gonna do to reduce your patient's bleeding risk whilst also protecting them from ischemia. This has shown that, um, that guided and unguided, and especially unguided. In the Talos ML trial, MI trial was safe. So essentially you have people that have had ACS. They're on aspirin and ticagrelor. After 30 days, um, they can switch them, um, and de-escalate them to aspirin and Plavix. So you're still protecting ischem for ischemia, but also lowering your, your bleeding risk potentially there. Also, um, the thought being there that, um. You know, do you need to check, you know, a P2Y12 assay? This proved that you did not. And, um, that's been proven to, to be safe and beneficial. And, uh, aspirin monotherapy, that, you know, really the, the big trial that looked at that was Smart Date trial. Um, after 6 months of DAP they put people on aspirin monotherapy after MI after ACS and compared it with 12 months of DPT, and it was, uh, it showed harm. Um, just, uh, uh, kind of, uh, you know, belabor that point is just a few of meta-analysis that I've shown here show that really aspirin has not been, uh, after monotherapy is not helpful. There's no difference in bleeding or an increased risk of bleeding and more, uh, ischemia. Finally, just to, to go through the thing that I think is most important and, and fun lately is extended, uh, uh, extended monotherapy of B2Y12s. The important study to mention is host exam. So it looked at patients, um, about 5000 patients, and it randomized them to either Plavix or aspirin 12 to 18 months after PCI. Uh, 72% of those had ACS, and it showed an improved, uh, improvement in MAC overall, as you can see on the right side with no difference in bleeding. Smart choice 3, similar idea here is that as, excuse me, Plavix monotherapy led to about a 30% lower risk for the composite outcome in that study, ischemic outcomes, and there was no difference in major bleeding. Stopped at 2, ACS, so they did a 5 year analysis, the two studies we talked about earlier, and they showed that clopidogrel monotherapy was superior to aspirin beyond 1 year, 23% lower risk of MACE, and then about a 40% reduction in MI which drove that reduction in MCE. That's a, a, a gigantic number. No difference in bleeding there. Another late breaking sky, uh, study just to mention here is, um, they looked at about 5600 patients that were very high bleeding risk and high ischemic risk, which is very important. One year post PCI after AAAT, and Plavix versus aspirin monotherapy showed lower rates of thrombosis and lower bleeding events, and that was regardless of high bleeding risk or PCI complexity. I put them in sort of 4 groups and. Um, we saw the big benefit from people at the highest bleeding risk and the highest ischemia risk. Um, this is just, uh, uh, the, the next thing just to mention is, you know, it wasn't really, um, uh, studied before whether extended Plavix monotherapy versus DPT, um, in high bleeding risk, high ischemic patients, what was best there, um, and, um, basically, um, the Plavix monotherapy was non-inferior in terms of MACE, and there was a, um, non, uh, excuse me, there was a relative risk reduction of about 26% overall, uh, for MACE events. Now, um, you know, how are we gonna, you know, parcel this out? Uh, the way I use it is I use two scores. So I use the DAP score to think about ischemia. I use the precise DAP score to think about bleeding, and, you know, that has been well validated in a lot of studies and essentially you can use this precise DAP score, um, that you see on the right side there. You can use that to stratify which patients might be at higher bleeding risk. Um, the way I look at it is anyone with a precise DAP score of 25 or greater, essentially, they don't need to be on any sort of extended DAP beyond 1 year. And those are people that, you know, whether it's 3 years for stable coronary disease, 6 months for ACS, I'm gonna really look at putting those people probably on an anti, uh, excuse me, P2Y12 monotherapy. Uh, my key takeaways for you guys, um, are, you know, after ACS, and, and, you know, this is something everyone probably knows, but again we've talked about how clopidogrel sometimes is, uh, is still continued, um, uh, or used after ACS really it's gonna be tagrular pressoril initially. Very few patients benefit from extended dapt. So if you see someone that's been on it a year and a half, take them off, use your risk scores, even if it's a high ischemic risk. Um, I would, you know, argue from the data that they need to be on P2Y mono monotherapy. I think that, you know, maybe clopidogrel would, you know, give you that sort of nice, uh, benefit potentially without that huge bleeding risk that we know you get from DPT, and we've proven that you don't have that bleeding risk with Plavix monotherapy after, uh, 1 year for ACS, for example, or 6 months for stable disease. And then, uh, overall, 3 to 6 months of depth is probably OK for most patients. Should definitely be the, the default and high bleeding risk people, uh, precise depth score of 25 like I mentioned. So I would stop the aspirin, continue a P2I 12. You're still getting that ischemic benefit without that increased bleeding risk that we mentioned. And then for patients who've tolerated DAPT with Tacarior, if you're feeling brave, you can transition to Tharoor monotherapy after one month. Uh, I don't do that a lot. Uh, it's mostly just talking to my patients and, uh, they say that sounds scary to me. I say, I agree. So we haven't done it a lot, but it has been, uh, proven, and I think it's a really nice way to get around that ischemic burden without, with lowering the risk. And then when you're transitioning patients, you're de-escalating. Clopidogrel is acceptable, definitely 16, 6 to 18 months after ACS, um, and with CCS, you know, the uh, chronic, uh, stable angina, uh, with a PCI, and that's when you use those de-escalating strategies. You're gonna get beyond that initial, you know, kind of danger zone of 2 months. And um I mentioned here that DAP de-escalation of Plavix, uh, plus aspirin reduces bleeding risk and a similar incidence, uh, with a similar incidence of ischemic events versus standard AP. So in a lot of those patients, especially high bleeding risk, no excuse for them to be on a prolonged dapt, and short dapt is really well tolerated. And then, again, my big takeaway from this, which I've started doing a lot, is really consider choosing Plavix over aspirin for chronic antiplatelet therapy beyond that 6 to 1 year mark. I think that's me and that's any aspirin investors out there sorry to ruin your day. uh, thank you guys so much for having me. Published Created by Related Presenters Brian K. Mitchell, MD Cardiology, Internal Medicine View full profile
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