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Antiplatelets - High Bleeding Risk/Single Antiplatelet

Feb 19 | 12:30 PM

Dr. Abhisheka Tripathi: TICAGRELOR is an all season antiplatelet without higher bleeding risk with higher efficacy Dr. Sarath Chandra: PRASUGREL is the preferred Antiplatelet given for his risk profile! Dr. C. K. Ponde: Clopidogrel is the safest choice amongst the three options

[Music] i would like to request dr janandra singh i think he's already there to introduce the speaker doctor please party is uh uh working as an international cardiologist at uh uh hospital uh at uh uh that is he has done his mbbs in 2002 from gst medical college kanpur and don md from from busy medical college in 2007 uh he has done his dna cardiology from hospital and medical thesis institute in italy and presently he is associated as concerned called central g medical research center new delhi for one year he also the experience of uh assistant professor of pedagogy at the nizam's institute of medical science uh hyderabad from april 2012 who met john 14. so the and our next figure is dr sarat [Music] is one of the most experienced international cardiologists from india yeah he had completed his dm uh from pga chandigarh in the year 1989 currently he is working in hyderabad he is one of the early internationalists of india and did first us closure of congenital heart disease in hyderabad and also the first case of uh in 1994 he has performed thousands of uh coronary angioplasties and has special interest in the lapman intervention uh he has performed for foreign international abroad even in china and vietnam in 1998 and 2004 respectively he was the chairman of the national international council of india during the year of 2008 and 2009. he was the editor of indian heart general from 2012 to 2014. he was the president uh elected in 2017 and president of cardinality society of india for the year 2018. uh our next uh next speaker is dr c pandey from mumbai uh he is the gold medalist throughout his uh ug and the pg area uh he has done the fellowship in international cardiology uh fscc fas app style uh fpsc fcsi fi fi sc and fi cc uh he has uh done his electrophysiology from brisbane australia uh from 1993 to 1997 he has uh he's respect of uh many hours like uh fellows about 1995 he has up to 100 publication in various national and international centers and he has delivered more than 500 lectures in various national and international conferences he has received an inspiring cardiology of india award by the economic times in 2020. currently he is the vice president of indian academy okay is it visible now yeah it's visible now we should go ahead please fair enough make it full screen it's visible yeah sure so uh thank you so much thank you so much come on baby for giving us this opportunity and the most difficult thing you are you have put me against dr chandra under whom i was under training in nizam so welcome sir good evening uh so the topic today as we all have discussed the patient profile 65 year old diabetic hypertensive 66 kg weight weight has been given very precisely more than 60 age has been given less than 75 to make it more uh discussion oriented there is history of coronary angioplasty to led with deaths seven months back on copper copper aspirin with recurrent mild hematuria maintained hemoglobin workup revealed bb bbh gfr remains around 60 so the wrong question is patient who is already stable with some history of hematuria bleeding uh hemodynamically stable no significant anemia patient on tropidogram aspirin within one year of angioplasty should be changed anti-platelets or what should we continue uh with aspirin global or should we change so my choose would be that why this patient came to follow up was it a regular follow-up was there any ischemia some worsening condition anemia was already mentioned it was not there so other considerations should be taken into a picture my take would be i would switch from aspirin and ticarcular combination i will attach the reason one by one as we all know the uh nascent platelets reticulated creatures they are higher in granules and they have very high reactivity than older patriots and they are mostly associated with cardiovascular disease and events if you see in healthy subjects the number of activated platelets are not and number of granules are not that high if the patient becomes unstable like and steaming and when progressing towards stimi the number of immature platelet traction it grows significantly high why it is important because we have to see which are the molecule available which works more precisely on immature platelets glamorous waters if you see the mechanism of action of dichotomous versus the thino pyridines you know parietans they're irreversible they bind to adp p2 vital receptor whereas ticarchiloid reversibly binds so it is free to remind again and again to different atp uh if we do white vital receptors not only that trigger load binds to p2 vital vital receptor as well as it inhibits ent1 transporter so what does it do it inhibits the uptake of adenosine and makes it more and more available which helps in cardio protection visual direction further inhibition of platelet aggregation modulation of inflammation it also causes dyspnea and improved illusion function so we can see technology doesn't only act with p2 vital receptor inhibition also it causes more and more availability of adenosine adenosine so uh now if you see i'll skip so because the only molecule out of the brussels and tropido which is not a program it doesn't need liver for um it's for activation so it is not dependent on c2p2 um cytochrome p2c19 system for its activation and this is why it is important because in asian community we have uh pleomorphism of the c2 cytogram p2c 19 uh enzyme so because of the preomorphism some people are they're rapid metabolizers some are late but i've been asking some are intimidating metabolism and depending on that the availability of this you know paradigm varies from person to person in asian community whereas whereas uh ticket reload largely remains in uninhibited because of this cytochrome system here you can see like if you see the uh thino pyridine versus the midi dose of uh initial binding like when you have those given the dose within 30 minutes this binding is there both in both the groups thinner parity as well as in decorative group in 12 hours time what happens that because of this repeat binding and reversible binding developer keeps binding to nascent and uh new lastness and platelets however by 12 hours time the nation binding operators decreases in theoretical paradigms and well this is the time when chicago is given again after 12 hours 34 hours once the peak effect of the dose is draining off you can see that again the binding of nasal platelets once those are inhibited that is besides the point in acute acids once the nasal preachers are being generated again and again the binding remains more complete with tica tilde complained compared to thino pyridines so detectors superior to plasma as have been seen in uh pharmacokinetic data that compared to plasma guild if you see the non reticulative site with natives both are equally effective but if you see nasa and platelets they have it periods ticker block is far more effective than transferable however these are the pharmaceutical connected data now once daily dose is insufficient in patients with high uh platelet activity here you see the blastocoel is being given daily dose at the late uh part of the plastical dose the activity of platelet activity again goes high whereas even during native space also the effect of uh plated activation is low so uh this is to summarize like the reversible reversible binding is there particularly not with your pyridines and it is active without metabolism and the mean half-life remains around seven hours for the active drug because there is no product so what is the confident factor t like trigger when we are using trigger glory we are all using it without too much consideration when we are using uh plasma wheel we always keep counting is less than 70 weight more than 60 there's no history of any stroke trauma or ic anywhere in the past if it's any kind of stroke also while using triggers we don't see much even if patients thrombosis is just four hours back we are using even if patient has been loaded with clopidogrel we are using so there is not much consideration not much fear factor around trigger load as much as it is around pressure so trigger is a broad every um road applicable antiplatelet which can be used in ac expression across the reach whether patient is being managed medically or intervention angiography diagnosis androgyny has been done or not this line of management has been decided or not we can use chicago invariably in patients with moderate to high-risk acs patients where the risk of ischemia is high again it can be used irrespective of the line of management however is recommended only when the pci has been decided and the pcs only in the pci setting not in the medical management line now again trigger shows decreased uh cv modality versus copy downgrade in plateau however password has not demonstrated decreased cv modality the mi risk was looped in triton tv 38 and trials is easiest but the mod city modality was not significantly lower again the another benefit ticker block can be used beyond 12 months like in pegasus um tv 54 it has been seen it can be used in 60 megabid up to 36 month time also rasulullah has to be used for one year the data is for one year only and uh shows less distant thrombosis compared to cropiogram in uh rct as well as real world um evidence also so as we have mentioned tikkablog can be used in wide range of acs patients irrespective of their line of management however in brazil mostly in titan tv 38 if you see it was being given in cath lab after angiography was the diagnosis was known that if the patient doesn't need uh bypass it was being given and the contract and contraindication as i mentioned we have to see the patient age if it is more than 75 you can't use if the weight is less than 60 ideally should not be used in india we are using five milligram also sometimes and contraindicated if there is any previous history of even skimming stroke is there it is contraindicated so we have to see all these things but in because you need not to go for this so this is just to summarize like if patient is having acs there is no contraindication particularly please use it yeah in classical you have to see the history of tia stroke need for capg coronary anatomy medical management versus non invasive management weight age and all these things pre treatment corporate growth symbolized or not so all these things you have to take into consideration before the loading before loading the patient with uh plastic gear so it makes life easy with technical order compared to plastic but when you're starting also while managing in long term also ac's guidelines it has class one recommendation for the patients uh to use ticago in acs patients with moderate to high risk of ischemic events so in all patients with moderate to high risk of ischemia it can be used uh tiger can be used plastic is used only when the patient has been planned for pci or in patient previous acs who are not thrombolyzed being managed medically and now coming up for um angioplasty tropidogram is used only once the trigger grid rod or plastic wheel cannot be um used similarly the latest esc guideline it mentions dragonglass preferred p2 by 2 innovators in respect to a management study as i mentioned like if acs patient is there whether medical management invasive delayed um invasive anywhere we can use figure neuron prostagland once the pci is intended then passable can be used that time classical detector both can be used but we have to make sure that it has been studied mostly in the pci setting so the recommendations are there for the pci setting only and uh for other things like the dpt duration the dbt duration for uh proper toggles can be used beyond 12 months regardless can be used beyond 12 months up to 36 um months hour with plastic there is no data to use beyond 12 months so if you see the benefits of compared to topic in plateau the trigger ground has been shown to decrease both composite endpoint of cv death nmi as well as cv death individually and am i indivisible however in time and triton 38 the composite end point was decreased out of only reduction in mi there was no reduction in cbd the mi was significantly decreased compared to clopidogrel so the non-capg uh related major grading was high in both chicago as well as corporate of classical compared to tropidogram however cbc rated measure breathing was high with plasma grid fatal overall bleeding was high with plasma wheel it was not high with trigger glow intracranial breathing was not rested not recorded in patients with transfer girls so it cannot be compared here with chicago so it is approved for long term more than 12 month protection as we just mentioned in pegasus um db54 study now uh for coming to strength thrombosis in platinum invisibility it was seen that strength thrombosis was significant 36 percent reduction was seen in instant thrombosis compared to clopidogrel different distance thrombosis significant reduction revival or definite significant reduction and in all possible prevalent definite there are significant reduction was observed over one year a year period compared to propagate so the timing of strength thrombosis like even till for the first 30 days for first one month in subacute distribution thrombosis there was 40 percent relative risk reduction was there up to 30 to 36 30 60 days like late eastern thomas is also 52 percent risk reduction was there so this is the reason where we will consider even if patient is stable if the patient is less than one year fantastic patient is a topic you may still consider shifting the patient from uh clopidogrel to tickle neuron zero strength thrombosis was observed in patients with trigger while in copper together around nine percent thrombosis uh was observed this is a small study now coming to the uh bone of contention the last study is react five which pitched tiger law against uh plaster grill and the plastic was shown beneficial as far as the mi reduction was concerned and distant combustion was concerned but if you see this study in detail you will find that the in the stemi patient both the group were randomized and they were loaded with trigger together beforehand before angiography however it and steaming trigger was given beforehand however was given after angiography once it was decided the patient is going for engineering now angioplasty okay so i'll just finish so if you see in this study again there was out of nine uh 85 patient 1.3 percent they did not receive ticker neuron however in practical arm 13.9 percent they did not receive uh brussels so the exclusion rate was much higher in transitional group compared to trigger growth finally up also if you see around one point one percentage represented from safety analysis however in last you'll get eleven point six percent were exploited from safety analysis so when the exclusion criteria is exclusive number of patients was so big difference was there it can skew the entire result of the study am i again we can see my difference was there definitely distant thrombosis difference was there primary endpoint difference because of these two factors were there but this from any cause was same stroke was same in both the groups and the uh major breeding two to five was also same in both the groups there was no major uh difference so the limitation the major limitation of the isa react file uh was that this is an open level study conducted in two countries our plateau was a blood double-blind placebo-controlled study conducted in 40 countries there was a disparity between if you see the end points if you see the major study of transgender like which was titled db-38 versus isa react 3. the ischemic event was 10.7 percent time with 20 38 here it was only 6.9 percent however as far as the trigger growth is concerned in plato as well i said three uh in assad five in both studies the ratio that percentage was saved 9.3 versus 10.2 percent so somewhere because of this open level kind of study and the randomization with sealed envelope and the quality of follow-up was also telephony follow-up mostly there was the bias cannot be excluded completely this may be the reason why the scheming events were probably reported lesser in uh isolate five or plus two grade compared to the article then again for safety normally it is considered the molecule which is uh potent antischemic effect will have more bleeding however if you see here the significant number of patients were excluded in prostaglandin 11.6 percent compared to only one point one percent integral group before you need to wind up yeah so i think if uh uh unique is going to include this isa react right somebody as we all know trigger group has an ease of using we can use it in any given number of patients the number of contraindications are very less post-traumatized patient already loaded with uh take a closer documentation we can use it safely irrespective of line of management we can use in these patients it decreases cb modality mi as well as strength thrombosis compared to proper occurrence so in my patient in in my choice the i will switch this patient from aspirin to operator to aspirin ticker thank you uh thanks kamal sharma for giving me this opportunity i appreciate my my old friend and nizam's institute i must say you done a very good job in this with regard to this subject now let me share my screen okay you're able to see my slide okay you're able to see the slide right right right okay all right you know the case details that were given to me are slightly different from what have been given to dr abhishek i have been asked to speak in favor of prosecutor in this particular situation so let us see what exactly are the case details given okay right here you have a 65-year-old diabetic hypertensive who presented with and stem now when you say a diabetic hypertension you are straight away saying it is a high risk patient his weight is 66 kilos which is not an issue with prostaglandin or with any of the other tracts he had past history of coronary angioplasty to austral led which is a very important location rather dangerous location of the state which was which has been implanted in the past the des was put in the australian three years back and he has been on clopidogrel and aspirin all these days and now he presented with amsterdam which means that there is some kind of resistance to aspirin and cropidogram this itself is a very high risk feature as we all know very well he gave history of two episodes of bleeding in stool which is stated to be due to piles but his hemoglobin has always always been normal now what is the importance of that now we cannot really say what is the cause of the bleeding we don't have more details obviously this patient has to undergo upper gi endoscopy and later a lower gi endoscopy if there is a need and did he have black colored stools or did he have fresh blood depending on that you can take a call on which investigation you would do first so but at the same time the hemoglobin has always been normal which indicates that probably the bleeding which the patient had in the past has not been probably a major bleeding and his egfr is 60 ml per minute which indicates that it is a fairly acceptable renal function and we know between these three drugs there is no issue in relation to kidney function when it comes to usage of any of these three drugs in fact with chicago or it is said that if the patients had normal renal function they did not show benefit with chicago over clopidogrel as given in the old plateau trial to which abhishek was different so the question is which pitot inhibitor would you use in this okay now let me show you a comparison comparing table between the four p two by twelve digits which are available in our market today the clopidogrel grassroots law and cannula are the last one to join the bandwagon the clopidogrel and procedural are irreversibly binding agents while titaglar and gangular are reversible clopidogrel and prasugrel are pro drugs while the other two are not the half life is about seven hours with crossover and chicago or it is eight to twelve hours type of binding is competitive with flopidogrel and prasugrel while it is non-competitive with decathlon the root of administration is world for most of these drugs except cantaloupe and we know clopidogrel is can be given once daily or even twice daily prostaglandin is almost always given once a day decagon is always given twice a day now onset of action is rather delayed with clopidogrel of two to eight hours on the other hand with crossover and ganglor it can start as early as 30 minutes and with candy lord within two minutes now the if you want to compare procedural to uh lopido girl this study one has to look at is the triton tv third yet this is a fairly old trial but it is a very modern trial in the sense it is a very properly done trial it is more than 10 years or 15 years old now and let us look at the recollect the date of right on tv 38 this is published in 2007 raw sugar versus clopidogrel in patients with acs this patient of ours is a case of acs and it was it randomized thirteen thousand plus patients six thousand to practical and six thousand to flopidogram and they were followed for six to fifteen months and the primary endpoint is death from cv causes non-fatal mi non-fatal stroke safety and point is major bleeding now the results show that the primary endpoint which is a combination of cv death mi and stroke is clearly in favor of crossover twelve point one percentage points with flopidogram and nine point nine percentage points with and the primary efficacy endpoint is what i just mentioned okay now if you look at strength transformations there is a huge benefit in relation to uh strength thrombosis when it comes to usage of prostaglandin significant reduction in the procedural group with the rate of strength thrombosis it is 2.4 percent with prostagl and 1.1 percent with 2.4 percent with glopidogrel and 1.1 percent with prostaglandin which is statistically significant now look at this balance of efficacy to safety and here again procedural scores over clopidogrel major bleeding was observed in two point four percentage of patients receiving crossover and 1.8 percent of patients receiving lopidogram now you need to look at the diabetic subgroup results in relation to triton tv 38 because our patient is a diabetic patient and you can see here the procedural reduce the rate of primary endpoint by a much greater percentage point it is almost five percentage points less compared to chlorogram so you have a diabetic patient rashford clearly scores over lopidogram when it comes to treating the patient by perfecting this means that's what we most of us do when the patient presents with and stimming as it is 17 percent versus 12.2 percent when the whole group is taken of course there is a benefit but when you take this diabetic subgroup the benefit is even greater and very glaring now if you see the timing major non-cabg bleeds there is no significant difference between global growth so procedural therapy in patients with acs with scheduled pci shows that significantly reduced rates of ischemic events including strength thrombosis increased risk of major bleeding including fatal bleeding but the overall mortality did not differ significantly between the two groups benefit was much more significant in diabetic patients particularly if they are younger and male patients now when we want to compare it with titan obviously you need to look at the data of iso react 5. unfortunately all these years we have been taught and most of us interventional cardiologists believed that prasudrail is a more dangerous drug than chicago rather titan or is a more safe drug the push given by the marketing forces that b was much greater with chicago and therefore ticagler has become very popular all over the world including india and indian doctors as you all know they play for safety more than anything and that's how the gagarin has been very popular in india but the data from isa react 5 is what you should really look at it there are limitations of iso react file as exemplified earlier by abhishek but let us look at the positive points of this particular trial intra coronary stenting and anti-thrombotic regimen rapid early action of coronary treatment fire now earlier we were always comparing plateau data with triton data this is not correct you know you do not know really what is the type of patients that have been randomized and comparing the data of one trial to another trial uh just because they have been compared to flopidogram is not correct the correct thing to do is to compare a try is to look at the data of a trial where digital or is compared to procedural and their patients are randomized on one to one basis and you can see here that this is an investigative initiated multi-center randomized clinical trial it was conducted to compare the efficacy and safety of the kaggler and brussels again in acs patients which is very relevant to the patient data that is given to us tiger law versus practical in patients with uh coronary syndrome published in 2019 very decent trial now you can see here that if this is not a small trial once again there were nearly four thousand patients who were randomized in this uh 2002 procedural arm and 2002 diagram and you can see here rasu girl has pulled over the private endpoint once again in the composite of death am i stroked and safety and point b uh bleeding and you can see here that cumulative incidence of safety and point once again there is not much difference crosstalk has nominally nominal greater advantage over tickler but this is not statistically significant the incidence of primary endpoint was significantly lower among those who received prasugrel than among those who received dicaglot incidence of major bleeding was not significantly significantly different between the two groups now uh if you look at this data the cumulative incidence of primary and point at one year 9.3 percent versus six point nine percent with classical a primary endpoint event occurred in 184 of 2012 patients who were randomized to titan law and 137 of the patients who were randomized to russograph and the cumulative incidence of safety and point at one year five point four percent versus four point eight percent now to further look at the data of iso react five the primary endpoint as i said is nine point three with tiger angler six point nine with brussels i i take it much lesser time i you know just give me a couple of minutes but i'm almost close to completion death is lower with prostaglandin mi is lower with prostaglandin stroke is nominally lower with prostaglandin definite or probable strain thrombosis once again is lower and the the combined endpoint is clearly in favor of crossover contrary to what many of us believed that it would be more likely to be with prosecutor was not the case when you really looked at it the bleeding events were less with procedural compared to tachagon definite strength transverses also was nearly 50 percent less compared to uh digalot now uh among patients who presented with acute country syndromes without without std elevation processing was superior to tigandrot with respect to composite endpoint of death mycolon fractional stroke fewer microline functions in the procedural group than in the tiget lab group this is not just the data of iso react you can see the data from some more slides which i am going to show you this is the regular trend that the chances of michael information are less in the classical group than in the dicagra group this is the substudy of steamy patients in the isolate i saw react included a wide variety of patients of acs but when you look at the stemi subset of iso react trigger was associated with higher incidence of michael introduction now classical is a preferred antiplatelet agent in primary pci stemi diabetes mellitus with acs recurrent acs violent lobito grain and risk for strength thrombosis now out of these four criteria three are easily correct in relation to our patient he's a diabetic he developed acs violent lopedogram and aspirin and because the stent was located at a very important point he may be running a risk of strength thrombosis or a severe instantly stenosis which may be making him more prone for events so our patient clearly is a case for anti-coagulant i'm coming to the last couple of slides this is a study from leeds uk it's a real world study which compared a huge number of patients who were treated with clopidogrel rasugrill and taglar and prasad is associated with the lower 30 day mortality compared to probiotogram anti-cancer now this is another data from about nearly this is a meta-analysis of seventy thousand patients of whom forty thousand were on either uh dicagliar and what did it show it showed that raw signal shows greater reduction of cv mortality by 15 percent and 18 percent compared to problematic law respectively prior signal was more beneficial than reducing mi base and definite or probable strength thrombosis than titan and lopidogram thirty one percent grant of reduction instant thrombosis uh the i think the since the time is nearly over i will close my talk and if any questions are there we can thank you very much thank you so much sir we would like to request dr c keep on it everybody all speakers are kindly requested to remain in time because we will have international speaker also they will be having problems please you kindly understand please thank you just sharing my slides quickly are you able to see the slides yes sir are you able to see the slides yes hello yes sir perfect perfect sir and can you hear me well thank you yes sir yeah i think i think uh we have heard two star wars here uh before me and i hope that i make some uh my simplistic slides will make us some bit of sense in these slides which i am going to show so i think the case scenario i am correct with uh kamal if i'm wrong uh 65 year old diabetic hypertensive weight was 66 kg egf was 60. he had a pcie video seven months ago i think that was given some different case scenario i'm not so sure was on dapt with aspirin or clopidogrel and presents with mild hematuria he's investigated and the found and the cause is found to be bph that is what was my case scenario am i correct yeah that's correct okay fair enough so what we don't know what was the clinical setting was that acs or ccs the pci was done with acs or ccs and what was the complexity of the pci and whether he had single vessel disease or multiverse surgeon those are the variables which are blinded to us purposefully by our dear dr commercial so let me take frequency and prognostic impact of breeding events in this adapt day study nine percent readings were chennai and in the last past two decades the ischemic events because of better and better p20 inhibitors have reduced from 18 to 9 percent hard almost but the bleeding has increased because of more potent p2 by 12 inhibitors that what are the problems with attack the problems with adapt are higher reading risk of bleeding is continuous and exceeds the ischemic events risk 30 days after the index pci breeding events increase the risk of ways further and any major bleeding increases mortality increase so the case in question is not really about aspiring copyright or neological is about balancing the risk of bleeding versus the risk of ischemic events and that is the bottom line so why bleeding increases mortality because measurement leads to transfusion there is prolonged storage of transmission raised to activation of inflammatory cascade and of course because of breeding you may land up in seizing or stopping the dapt for a short duration exposing the patient to the risk upstream from us now the main question and the fundamental question and the billion dollar question here is do we need a dapt beyond six months in a patient who had a pci with the ds forget the setting acs ccs doesn't matter do we really need that beyond six months guidelines say whether it is stable coronary artery disease or acute cardiac syndrome if you have a high bleeding race or a patient who bleeds six months of dapt is just about adequate you don't need to give dapt beyond six months so indeed choosing the duration of dapt was the art of medicine where the science did not exist until five years ago until the stop depth trial came but now we have science and i will show the science so when you compare ischemic risk for this let us say you have an acs you have taken during pci pre-loading you are not done etc etc you have done re-stratification you are done breathing prevention by adapt intensity ppi counseling example the patient yet lands have been bleeding when the patient lines up in bleeding like our patient has you have to shorten the diet so there is no question of continuing the death in this patient beyond six months you have to de-escalate that so you cannot give you cannot think of giving aspirin with ticagrelorn no question that question doesn't arise what question is if at all monotherapy which monotherapy so is our patient as is at highest chemical risk so if you have two or more of these factors he is high ischemic our patient is only one factor that is diabetes so he has moderate ischemic risk do we know the complexity of our pci in this patient no we don't know whether there were three students implanted two legions treated total length was more than 60 we don't know that even assuming it was there look at this line beyond 30 days the risk of ischemic events geometrically comes down and reaches nadir by around four to six months whereas the degrees escalate remains so it comes down beyond below 30 days but remains higher than the ishthimikris beyond 30 days so the point here is we are at six months after a dapt in a patient who had no ischemic events in the first six months and has landed up in bleeding which is although minor is recurrent so now when trials were done comparing the hypothesis that three months was non-inferior to 12 months succeeded three months non-inferior to 12 months succeeded six months non-inferior to 12 months succeeded on the other side when you tested a superiority hypothesis that 24 is superior to 6 months failed 12 months superior to 12 months failed 30 months superior to 12 months there was a lot of problem in this trial we all know that that's right and then 36 months superior to 12 months failed so in this the topic trial replacing p2y2 individual with tropidogram one month after pci in a unselected group of patients unselected mind you ladies and gentlemen with without considering the complexity of the index pci without knowing what kind of acs drop positive top negative after one month with the patient is one month event three shifting the patient to clopidogrel from a more potent p2y12 inhibitor reduces breeding without any additional ischemic event risk this trial opened the pandora's box and then trial after time look at this telos ami releases 2021 acc ticagrelor versus copyright is stabilized patience with ami so patients remain stable for 30 days shifted to aspirin clopido what happened the bleeding risk came down the cumulative incidence of composite endpoint of death and my stroke came down so the conclusions was in ami patience no adverse events after de-escalation stop that time sure among patients undergoing pci one month of that followed by clopidogrel monotherapy compared with 12 months of that with aspirin and coppedocryl resulted in significant lower risk of composite cardiovascular breeding events mind you these were not the patients who bled these were the patients who are otherwise stable irrespectively they are shifted to cooperative knowledge here there is a patient in my plate who is bleeding recurrent although minor breeding hemoglobin is maintained and the cause is bph not a sinister cause host example aspirin versus chromatography for chronic maintenance therapies what happened here the aspirin reduced had higher event rates bleeding wise and higher eventually ischemic wise now dr tripati might come and say why not stop it all monotherapy let me compare let me compare twilight look at the twilight bleeding risk 7.1 percent tikka versus sunscreen and four percent tikka alone whereas clopidogrel alone the bleeding risk was 3.7 percent i agree that these were higher especially much higher expression than the telos in my time however the conclusion was clopidogrel monotherapy as compared to aspirin immortal therapy significantly reduce the risk of composite all-cause death non-fetal feminine stroke and re-admission also due to acs and bad type 3bd so please remember don't uh dumb trophied okay yet don't dumb trophies yet you can escalate you can measure your beating risk versus ischemic risk by this very simple pro chart in your clinic or in your cath lab what i will do in this patient if the setting it was of acs and a very complex pci has been done like left main all led one bifurcation with dk etc i would probably continue this dna which is going on aspirin and copyright there is no need to escalate the p2y2 because six months the patient had no ischemic event no strain thrombosis and i also know the cause of bleeding is minor is a minor breeding and the cause is not sinister like ca or uh gi cancer or something like that otherwise i will shift to clopidogrel monotherapy that will be my take so my final studies we know we have versatile tikka here we know we have aggressive tropido girl here here but the king will still remain the king and that is thank you very much we would like to keep this forum for open discussion yeah so the case the scenario had changed i don't know somewhere dr chandra but anything anyway we we the important thing was to understand two aspects one was single antiplatelet versus dual antiplatelet then we have the slides neelam so uh beyond what time we can stick to one and then if you are sticking to one which one of the three so dr chandra your take if it was supposed to be say only uh why not please unmute yourself sir say you're muted okay okay i'm here now you know what is the question uh did you say can you just repeat the question yeah if this angle if it was not for so a dual antiplatelet just a single antiplatelet why not press the grill well uh you know we don't have data with single antiplatelet therapy with prostaglands so i cannot really comment on that i am very impressed with tricangular monotherapy when i looked at the data of you know polite and one should not forget there is another trial called the chico trial which is very very similar to twilight trial and there also there was extremely increasing data in relation to titan monotherapy and tycho trial was done in acs patients so you know the days of you know using long-term dual anticipated therapy are more or less woven we all know today that it is the combination with aspirin that actually increases the bleeding risk particularly the upper gi bleeds so this is uh one point i would like to say that use after three months as shown in polite antico of a tiger monotherapy probably with prosperity if somebody does a trial then we can probably support it second point i'm very impressed with a relationship with these dual and creative therapies and during this years that it is not enough to say that if your patient has a bleeding problem i will cut down on one of the drugs or both the drugs or whatever it is also important to look at the source of the bleeding there is a very good data from poland where they had 6 000 patients of you know genital urinary bleeding and they found that most patients had some cause for bleeding this is the case with my own experience also so i would say instead of coming down on life-saving important effective antiplatelet therapy you also look at the source of bleeding and probably by treating it you can reduce the chances of bleeding in future it is a combination of antiplatelet therapy plus the source of bleeding that is responsible it is easy to stop the antiplatelet therapy and then reduce the chance of bleeding but then lurking very close behind closely around is a thrombotic event so all these patients who develop bleeding while unanticipated therapy they should be investigated thank you [Music] we want to understand better than all the available uh monotherapy and breathing points breeding source definitely should be valid like you most commonly see the gum bleeding and all and it is not because of the antibiotics because the overcome hygiene and the lower oral hygiene that is the mostly the source one question to uh princess like he said he will prefer to go with chromatographical monotherapy rather than aspirin anything else so uh we know regarding the resistance of clopidogrel in in indian community and it's a good amount this the the the percentage if you see varies from almost 20 to 20 percent across india so are you still uh content with starting global monotherapy after six months versus aspirin monotherapy after six months versus triggering more therapy after six months yeah uh that's a good question dr free party i agree with you uh i was given to support cryptography but but in telos in telos both these trials have shown unselected group of patients being de-escalated through propagal alone after six months the most important for factor year is after six months so six months patient didn't have any ischemic event and by six months more majority of the newer generation ds they get endothelials and ischemic events are very very minimal after six months of therapy so that is one point and second point is the in vitro resistance our own paper in 2009 first and 2016 um uh in in quite two respected journals showed that there is very poor correlation between the laboratory resistance versus the clinical resistance uh with two cropiograms that is my biggest problem so far so many patients to a laboratory they are not responding to club photography clinically they respond and the other way around so it is very difficult to uh choose a drug that way i think we should go by randomized controlled trial here and i would be very happy for a ticagrelor or monotherapy but i will not be happy to add another p2i2l inhibitor to aspirin beyond six months in this patient at any cost and with if the patient's copyright aspirin has worked for six months why not copy it over the alone will work after six months that will be my take so so that's two quick pranks sir two quick quick friends like we mentioned that after uh six months all the new generation this uh open to both princesser and uh so like we mentioned after six months the industrialization is good and we don't need six months uh i'm beyond six months but we know that there are the newly not that um old we have find the word very latest and thrombosis western thrombus is beyond one year also we are seeing in our practice also number one point this one side we are looking for a lesser and lesser duration of anti-matrix second side we don't if we aren't even sure how long it does really take in different different scenario patient number one number two twilight and taco they were all for the western population they were not for indian population number three we have really observed that after coming this chicago and prasada in picture there is the the this rate of least uh mace remi re-hospitalization and this unplanned distribution has really gone down so these molecules are definitely helping us if you see the real world practice your real world evidence so i think this everything should be taken into consideration real world evidence as well as the randomized control data i think i think if you ask majority of the interventional is the fulcrum i mean the the the majority of the opinion will turn in this case towards become monotherapy alone followed by cropitude monotherapy and followed by aspirin continuing aspirin crop protocol 70 by 75 oh that's fine i agree but i think in a patient if this scenario was to become three months i would stick to prasu as the alone one maybe won't you or won't you if it's a mild bleed uh if it's a recent recent mi and you want to do a single anti-platelet and it's a proximal austral led the kind of case that you said and it was not a gi bleed as dr conde was trying to point if choosing one would you still stick around with prasa grill and take off aspirin which acutely you know let me elaborate on this if you take a molecule to molecule i have no doubt procedural is the most powerful agent we have had our own experience like what dr pandey said a long time back at museums we did in vitro platelet aggregability testing and prasugrel you will be surprised to know that platelet aggregability can be as low as 0 or 2 percent are four percent in most creations and that happens in a very short time after the administration of the loading dose so what is important is that we all know that procedural is a very powerful agent chicago is also equally powerful probably but if you really look at the data of trident 38 the kind of strain thrombosis reduction with prostaglandin compared to clopidogrel is very impressive 35 reduction of strain thrombosis in diabetic subset so if you ask me a question that if you have to use only either practical articular i would go in favor of prostaglandin if you have to use only one track yeah i think for the sake of time we need to move to the next session we had a wonderful session thank you very much for highlighting and i think we brought out the important aspect of single antiplatelet which one to choose where is the evidence which patients to understand and believe as the high bleeder risk or low bleeder risk a mild bleed in a hematuria a high risk versus non high risk so that's why we try to balance it out the case scenario that one thank you very much

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