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Antiplatelet Therapy: Where Do We Stand Now?

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Welcome to this session antiplatelet therapy where do we stand now this is uh sripal bangalore interventional cardiologist and professor of medicine at nyu school of medicine i’m joined by my friend and colleague usman barber usman hi street paul wonderful to be with you and all of you on this important topic my name is uswan bauber i’m an interventional

Cardiologist at the university of oklahoma health sciences center i serve as a director of the cath lab and interventional cardiology look forward to this conversation so as uh you know cerebral had mentioned we’re going to talk about ant platelet agents where do they stand and you know sri paul when you and i were in residency in medical school this was a

Pretty easy question now you did a coronary stent and patients got aspirin and then one additional drug which is clopidogrel and uh you usually kept it on for about a year and now really the last 20 years or so it seems like we’ve been having a lot of studies a lot of evidence has been generated so you know why now are we revisiting this topic that seems to sort

Of never be put to rest yeah no great questions i think uh you know it’s interesting that over the last couple of decades that the paradigm has changed i mean we started by saying longer the better um because of all the stem thrombosis events which we used to see even after one year after a stent implantation so i think the question obviously is as anything

Change should we revisit this and i can tell you that i think our understanding of what’s happening i mean the balance between ischemic and bleeding risk in a patient is critically important to evaluate and of course i mean if you look at the ischemic risk for a patient who is undergoing stent implantation you know we’ve come a long way and we made significant

Changes in stem design if you look at our stem thrombosis rate i mean first of all if you look at the healing rates of these tents it’s much faster healing and less kind of inflammation etc all of these design changes have significantly improved the safety of these tents so no longer are we seeing uh high rate system thrombosis i mean nowadays the rate system

Thrombosis the first year is around point five to point six percent and after that it’s like point one percent so it’s it’s very rare to have stem thrombosis these days and of course the risk depends on the individual ischemic risk on the other end we also made significant progress in reducing other ischemic events for example we have more potent antiplatelet

Therapy we have better uh more potent lipid lowering pcsk9 uh we have the compost trial data adding anticoagulant steel t2 etc so we are really making an impact on reducing the patient ischemic events but if you look at the other side of the equation which is bleeding we know that our patients are getting older and so that is completing is higher so once

They get older they are on they also get afib they get on anticoagulant therapy the the more potent anti-platelets also increase the risk of bleeding so if i have to weigh the risk benefits of ischemic versus bleeding risk for the last two decades we have reduced the ischemic risk but i would i would say we haven’t done much in terms of reducing the bleeding

Risk the bleeding risk if anything has increased so i think this is the context that we have to look at and this is one of the reason if you look at both the accha and esc guidelines if you have a stable patients after stent implantation both of them recommend a six months minimum adapt i mean no longer it’s one year and and if it is and this is supported by

A number of randomized trials showing that if you go lower in stable coronary artery disease patients your risk of bleeding is lower but you don’t pay as much as a price in increasing the ischemic events uh but i must point out that there is still a lot of confusion and maybe let me ask this question to you uh the confusion seems to be uh based on couple of

These longer uh dap trials the the pegasus the dap trial where we kind of saw that beyond one year and longer uh the extending debt would not only reduce your stimulative events and put potentially non-stent related mi so what are your thoughts on this and why is there a lingering confusion and what should we do about this yeah well i think you know you hit

Um the the kind of nail on the head which is this nuanced understanding of ischemic and bleeding risk and that’s at the foundation of all of these conversations and part of this area has now evolved where we really think about these trials adapt is one pegasus is one themis is another where you’re actually seeing ongoing benefit with longer durations going

Out to several years of dual anti-platelet therapy and then one has to reconcile that with what you just mentioned which is guidelines telling us we can just go up to three or six months in stable patients and i think one way to think about those is number one what’s sort of the obligatory minimum duration of that what’s the minimum duration you need to give

A patient with these newer stents that heal in a more rapid fashion in a complete fashion i think the guidelines and the evidence clearly support that number is probably around three to six months and that’s what our guidelines say the second question that is still being sort of addressed now and is still evolving is who are the patients in whom once we get

Beyond that obligatory phase can we give additional ongoing anti-thrombotic therapy and still get a benefit and i think we’re seeing some answers to that patients who are compass-like patients who’ve had prior mis we saw in the dap trial and in the pegasus trial so there are certain patient phenotypes usually based on clinical criteria where we’ll get ongoing

Benefit if you extend anti-thrombotic therapy but at the end of the day you have to balance that benefit with the underlying risk of bleeding yeah i think that’s a those are great points i mean i think the uh the key take home is individualizing decision making and you know for stable coronary artery disease it’s clear that the minimum obligatory damp duration

Is six months and if if it is a high bleeding risk and if you have to stop earlier three months and even i think there is now emerging data on one month duration on these patients um maybe let’s just switch briefly to acs patients um you know acs has been interestingly i mean we talked about changing guidelines for past two decades ac’s dab duration has always

Been 12 months accha and also esc would say obligatory minimum is 12 months if you have a high bleeding risk patient you can go down to six you did the landmark twilight trial with roxanna maran and you you presented the acs upset as a late breaker can you share some insight into the acs subset and can you also talk about can we actually uh reduce the dab

Duration to shorter than 12 months in acs patients yeah that’s a great point uh street paul and i think as you mentioned the the one area that has not really been pushed until very recently is in patients with acute coronary syndromes and um the note the idea basically there is can we shorten the dapp duration the question becomes well how do you do it you

Can either drop the p2y 12 inhibitor and that has been investigated in some studies smart date and it was found to be actually potentially harmful so the alternative is maybe we can shorten the dapp duration by getting rid of aspirin and that’s precisely what we looked at in twilight and we had about two-thirds of our patient populations a little over four

Thousand actually had non-est elevation acute coronary syndromes and twilight was a cohort where we took patients who were at high risk so they had either clinical or angiographic features namely diabetes a long stent uh length implantation and all the patients got three months of adapt with aspirin into kabul or and after three months we randomized them to

Cargalore alone or continuing to cargill or plus aspirin and in the acute coronary syndrome subset we found that you could significantly reduce bleeding and you didn’t pay a penalty on the ischemic side so it suggested that in fact this could be a safe strategy you don’t pay a penalty in terms of harm and these hypothesis has really been i think corroborated

By the tico trial which focused exclusively into qmi patients and they had actually stemi patients and found essentially the same results to what we found in twilight you know so i i do think there’s an evolving uh paradigm change that might be happening even in acute my patients wherein we can withdraw the aspirin lessen the bleeding and keep patients safe by

Giving them a potent p2y12 inhibitor and i know uh you know you’ve done a lot of work in in pooled analyses and network analyses and uh maybe you can say what your kind of findings were when you your team kind of looked at the aggregate data in this area yeah no absolutely so you know we recently published uh meta-analysis network analysis looking at all of

The acs of groups i mean asking exactly this question i mean we i think all of us are by now are comfortable with the shorter minimal obligatory depth for stable patients what about acs patient so we had 14 trials over 31 000 patients and the results are very consistent i mean shorter damp duration three to six months reduced bleeding there was no increase in

Ischemic end points and so i think there is more and more emerging data uh to support uh shorter depth even in acs patients and of course the question is always like what do you do like what do you drop and in fact we published an analysis looking at what should be your treatment of choice after you drop after a short duration of depth should it be aspirin or

Should it be p2 y12 and of course as you know there is no hit to hit comparison as to which one is better uh these trials either dropped aspirin or dropped p2 y12 what we found was um of course this is an indoor comparison this was published in the american heart journal uh a month ago what we found was uh if you look if you if your intent for a given patient

Is to reduce the risk of bleeding if it is a high bleeding risk patient potentially just continuing aspirin after dropping p2y12 is a better strategy but if you’re if your patient is at high ischemic risk it’s potentially you should continue p2y12 and drop aspirin which makes into this sense but of course it needs to be tested in uh head-to-head randomized

Trial but you know that kind of uh gets me thinking about um you know we we’ve been talking about dropping aspirin in multiple different settings i mean if you have patients on triple therapy we recommend the minimum duration of triple therapy drop aspirin and so there is this growing notion that aspirin as part of dab may not be needed as previously assumed

Um so what are your thoughts on single-player antiplatelet therapy yeah you know i think it’s interesting whenever we have a new strategy in medicine we always start off with high-risk patients then you go to lower and lower risk patients we’ve seen that over and over and this idea of aspirin-free strategies started off as you mentioned in the highest risk

Patients namely afib and even needing triple therapy and it’s clear that in those very high-risk patients you can withdraw aspirin and patients do fine we have now pushed the envelope with studies like twilight global leaders and other to take patients without afib and dropping aspirin and we’re seeing consistent themes with or without acute coronary syndrome

So the question then is can we even get to the low-risk patients and as you’re aware there are studies that are have been published and are ongoing and are asking a very provocative question which is at the time with stent implantation you give aspirin but then right after that you just stop it and you just go into p2y12 inhibitor alone now those are very low

Risk patients and we’ll have to see what what the data shows my bias would be that i think we’re going to need some aspirin for at least a few weeks before we want to withdraw i think people have a hard time but you know this is how science moves forward um and uh as we kind of started this you know where do things stand i think where things stand is we’re still

Learning a lot we have learned a lot but this field stays exciting it’s moving um and i think there’s a lot more to come in the very near future yeah i think those two great points and specifically i think if you if you have a patient who is at high ischemic risk and also high bleeding risk i think the emerging data would suggest that the bleeding risk kind of

Trumps uh ischemic risk and we should try to do everything possible including you know whatever you can do ppis etc to reduce that risk of bleeding reducing the duration of triple therapy you know in terms of single line to platelet therapy up front i mean i’ve only used that in patients who have asthma and allergies and using a more potent p2 as well there is

No data on it but ivis guidance is key for those patients and and i think those are uh important uh definitely important considerations um let me ask you a slightly different question what you do in your clinical practice if you have a patient on triple therapy um and for whatever reason you’re using clopidogrel and you want to draw up aspirin are you doing

A platelet function study to make sure that you know it’s not a protein antiplatelet you just want to make sure if it is one antiplatelet it’s actually working what do you do yeah that’s that’s a great question so um there was a time not too long ago where i was doing a lot of platelet function testing but i’ve because of a lot of data that have come out i’ve

Kind of gone away from that so i will tell you uh as long as you’re on a directoral anticoagulant um i’m okay with them being on clopidogrel uh and getting rid of aspirin without any platelet function testing um in the absence of a direct oral anticoagulant thus far i really haven’t done clopidogrel monotherapy i have done calgalore monotherapy but i would be

Concerned about clopidogrel alone without either aspirin or a direct oral anticoagulant so in that context if i had to make that decision i would want a platelet function test so that that i think that’s uh it’s a very nuanced point and i agree with you and at least in my practice i haven’t dropped ask for at the time zero unless there’s some type of allergy

Really compelling indication you know where i cannot give aspirin at all yeah yeah i think you know those are the things that we discuss i mean i routinely do test i mean i get nervous with uh clopidogrel you know uh the rate of non-response i mean although you’re absolutely right there is just no evidence for routine testing but i only routinely test if i’m

Dropping aspirin just to make sure if there’s one antiplatelet let’s make sure it works um but i think um i think this was a great discussion i think we packed a lot of important points and i think there is emerging data just to summarize emerging data to support shorter obligatory minimum dap duration not only in stable patients but also in acs patients but

Um i completely agree with your point that we do have to individualize and i think the challenge is you know how to how to do this i mean we have so many other therapies when do we add anticoagulation therapy how do we follow an accomplished regimen so those are all uh important uh discussions to be had and i think more and more emerging data on potentially

Going with a single antiplatelet therapy potentially a more potent p2y12 monotherapy just like what twilight did and i think that’s a landmark trial which will have a significant impact on how we manage your patients any closing remarks uh what do you think of no i just want to say thank you i think this is a great discussion it is a lot to pack in a lot of

Different uh you know concepts to put in one but this is an exciting time i think and i think it’s exciting when we have uh newer approaches newer strategies newer therapies with evidence to help our patients so i think it’s good for us as clinicians and investigators and good for our patients to have newer ways to give them an overall clinical benefit and

Very much look forward to you know more data coming out and more discussions and it’s been a pleasure having this conversation with you thank you and thanks everybody thanks for joining us on this important discussion thanks you

Transcribed from video
Antiplatelet Therapy: Where Do We Stand Now? By Medscape