This presentation summarizes recently completed, ongoing or planned randomized clinical trials dealing with antiplatelet therapy, anticoagulation or both in the context of stable coronary artery disease, acute coronary syndromes, atrial fibrillation and venous thromboembolism.
So i will tell you what we do now so now mine is the last presentation in this what we call clinical trial parade okay so maybe you will survive this and after that there’s one more presentation by gzip rossano and he has to make up and after that we’re done okay so are we ready gentlemen in the back because then i will start the last presentation and in this set
So my topic is to talk about acs and antithrombotic therapy and what’s what’s coming up and what’s what’s new so to be briefed on that there were many trials investigating ad on antibiotic therapy aspirin replacement and aspirin free strategies in cardiovascular disease and event prevention so this is like the scenario i’m talking about so one thing is here is
The called gemini acs trial which was looking into patients with acs who were all on clopidogrel attack a goal or to replace aspirin with rivaroxaban baby dose two point five milligrams twice a day so it was testing rivaroxaban 2.5 b id versus aspirin and look at this number one they looked for significant bleeding there was no significant difference number two
They looked for ischemic endpoints no difference here so now there’s a big trial the gemini acs trial planned which will look into cardiovascular outcomes testing the hypothesis whether rivaroxaban is as good as aspirin or better in the setting of acs patients that’s a big trial okay so here’s the next this is something called the global leader study so this was
Looking into patients with stable coronary disease or acs in his stenting scenario and was testing the hypothesis whether short-term aspirin plus long term tackle or is better than standard treatment and you look you can see it here so aspirin was stopped in stable cid and sorry in both both treatment arms after one month but agricola was continued for two years
And this was compared to standard therapy at that time which is in stable cid dual antiplatelet therapy with so peter gulla for one year and an acs sorry for four yeah it’s tabled cid for one year and an acs with techical or for one year the results are out and to make it quick the primary endpoint was all cause mortality and nuke you wave am i and you can see it
Here in red you can see that the significance level was not met so therefore it’s quite simple this strategy after tech talk a girl or together with aspirin for one month in chicago for 23 months was not superior to standard treatment so this child didn’t make it meet its objectives so another one with tackle or this is now stable cid but high-risk patients high
Risk pci so here the question is asked whether tackle or plus aspirin for 12 months or reference strategy tackle or alone for 12 months after three months of fuel and depleted therapy is better so here we have three months of takigawa aspirin and then after that continued aspirin therapy or terrigal or alone we will see what that will what that was children another
One is adapt strategy in patients with increased bleeding risk and this is all is looking for bleeding and ischemic endpoints and this is the 12 designed 4300 patients who have acs or stable cid and they will receive one month of dual antiplatelet therapy and after that one month this is wither with a modern stand platform will be randomized to single antiplatelet
Therapy for additional 11 months or standard depth which is considered aspirin for one year and comparable for example for five additional months okay so it’s looking for one month dual antiplatelet versus six months of antiplatelet therapy in patients with high bleeding risk okay another one this is now in the diabetic patient this is looking for aspirin and you
Know that diabetics are not responding as well to aspirin as other patients so this is looking an see s patients weather double dose aspirin is better than normal aspirin in these patients okay so you can see it here it’s once a day aspirin 100 milligrams versus twice a day aspirin 100 milligrams in diabetics with acs to see if more aspirin has a beneficial effect
In acs patients this is not stable disease another one looking in stable patients with coronary disease is the themis trial this is looking for tech aguilar versus placebo so these patients patients have stable cid ca d and they do have the majority of them will have a low dose background of aspirin treatment and this is now looking in this patient population
Which is considered high risk if additional tech a goal or is superior to placebo treatment so pretty much is looking for dual antiplatelet therapy with aspirin and terrigal or against single antiplatelet therapy with aspirin in patients with type 2 diabetes and stable ca d and we know that there is a positive result we know though we do not know for the details
So this will be presented soon but obviously the strategy seems to have some positive benefit so we will we are looking for this this is interesting because to remind you aspirin treatment in patients with diabetes without ca d is not beneficial you know this so their little benefit in terms of event prevention but on the other hand more bleeding in this patients
So high-risk individuals without ca d with diabetes do not benefit from aspirin therapy because they have no bleeding events okay so what is new this is something completely new this is tackling glycoprotein 6 so this glycoprotein is important for the interaction of platelets with with ethros radek plaques and the interesting thing here is that the idea is that
This drug called reverse eped may inhibit the interaction of platelets with the plaque but will not have much impact into systemic hemostasis so potentially gives ischemic benefit but not causes bleeding so this is a very interesting things but you can see here on going face phase two trials so this is kind of early in the development but in very interesting
Concept okay so now topic for the triple therapy so this is about patients with atrial fibrillation and stent placement or a q coronary syndrome so you know that we were thinking about triple therapy in these patients because you have to have we’re thinking of having anti coagulation treatment with dual antiplatelet therapy the drawback of this is a very high
Bleeding risk so bleeding risk in this patient is almost four times as high as in patients not receiving triple therapy so what are the strategies so strategies were number one short and triple therapy that did work out use dual instead of triple therapy and use noack instead of v ka to reduce bleeding risk because of the safety profile so last year we had these
Two trials pioneer hf and we dueled pci and to make it short the primary endpoint was bleeding it was always major bleeding plus non clinically relevant non major bleeding and you can see here that in both trials these bleeding endpoints were significantly reduced in a treatment that was using dual antiplatelet dual therapy with no ak and one antiplatelet agent
So in case of pioneered was rivaroxaban 15 milligrams plus mostly takigawa and in rajul pci it was the bigger turn 110b id or 150 v id together was mostly clopidogrel but also some technical operations and in both trials there were there was a febrile oscar outcome was less significant bleeding however it needs to be mentioned that these trials were not powered
For ischemic endpoints these were powered for bleeding events okay then there was this meter analysis taking these two trials together with older trials like the wust trial and the ice a triple and they came up with this relative risk reduction 50% for all bleeding so this is major and as a major bleeding’s and non major bleeding’s and minor bleeding’s so but the
Concept showed benefits in terms of bleeding risk without signal towards harm and of ischemic events but again keep in mind not powered for ischemic events powered for bleeding events so these are the guideline recommendations or let’s say consensus papers so these are this is the north americans perspective so the american said okay given these data dual treatment
Which means anticoagulation with 1 and depleted agent so it should be default strategy and only in patients with high ischemic risk it should be triple therapy but on the other hand these are the european guidelines are the european consensus completely the other way around should be triple therapy and only in patients with very high bleeding risk dual therapy
Should be considered so same trials very different perspective and the reason while the europeans went this way was because they said well when number one we have a mix of patient populations with cid stable ca d and acs and number two trials were not powered for ischemic endpoints and we need more data ok and this does make sense although this is not statistically
Significant in the rajul pci in the 110b ad those were there were numerically more myocardial infarctions and most in thrombosis and that’s why it was said ok maybe we have to think twice so they were asking for new data and this is another child the augustus child which has a different design the largest of these of these trials four and a half thousand patients
With stable cid or acs and atrial fibrillation and these patients were number one randomized to receive a pixum and five milligrams b id so no dose reduction or vitamin k antagonist and then a 2×2 factorial design were randomized to receive aspirin or placebo by this investigating number one no aggressors vitamin k antagonist and number two looking for triple versus
Dual therapies a very smart trial and results were to be shown at the acc 2019 you know the acc was just one week ago one weekend last weekend and these are the results does this have taken from the new england journal paper so you can see in the upper graph that apixaban versus vitamin k was a swath warfarin you can see there’s a significant reduction again of
Major bleeding’s and clinically relevant non major bleeding’s this was the primary endpoint and on the other hand if you look at the lower graph if you look for aspirin versus placebo a very significant higher risk of bleeding in the aspirin group ok 2×2 factorial design the majority received clopidogrel and just some patients attack a cola or program if you look
At this you can see very nicely in these upper graphs that leaving out aspirin has a big big impact on bleeding risk okay so aspirin is one thing but when you consider that the grass before this child is very nicely showing that noack versus warfarin shows benefits of noack treatment versus warfarin and then in addition looks for aspirin effects on bleeding okay
The lower part is showing major bleeding’s and in the augusta’s trial also major bleeding’s which was a secondary endpoint was significantly reduced in the apixaban arm versus the vitamin k arm okay so this is now looking for death or ischemic events this is the ischemic endpoint again not powered although bigger not powered and when you look at this you do not
See in numerical difficult a difference so hazard ratios 0.93 so there’s no difference if you look at the lower part i have to show it with my hands because i don’t have oh i do have a pointer here maybe i use this you can see here so this is comparing a picture band with vitamin k tagging ists myocardial infarction stent thrombosis an urgent we’ve asked there’s
No difference but when you look and the aspirin versus placebo arm you can see here in the placebo non-aspirin arm there are numerically higher numbers of mi stents imposes an urgent revascularisation so again pointing out that some patients may benefit from triple therapy and not joules happy so i think it’s a great trial so there’s more coming there’s a trial for
Munich approach acs which is also using a pixum and his dual therapy with a pic 7 and cope integral and comparing with a classic triple therapy vitamin k antagonist aspirin clopidogrel with a shorter duration within patients with high has bled score and a longer duration in patients with lower has bled score so we’re waiting for this in the last one that’s coming up
Is the untrust af pci trial which is using a pixel sorry doc seban 1500 patients to be enrolled again comparing dual therapy with noack standard dose 60 milligrams a doc seban plus a pt y 12 inhibitor with classic triple therapy vitamin k antagonist v 2 y 12 inhibitor and aspirin and is estimated to be finished in june 2019 so this year we will have these results
As well ok different topic this is about reversal agents of nowak there are three principles we number one have an antibody against a bigger trend which is called eros it sum up we have a small bullet that fights kind of every antithrombotic agent it’s a small molecule it’s called syrup run talk and then there’s a truncated factor 10a which is tackling the 10a
Inhibitors which is called and excellence or different concert concepts and to make it short this is about the trials that we have right now when you look at this siripuram tech is in phase two so very early we have to see if it works out when you look at either it eats them up we have the full results of the phase 3 trial and either zoom up was approved by fda
And ema and index anette now the full cohort study cord is published of the and nexif or trial which is the phase 3 trial there is fda approval eema approval is pending but the c hmp recommended conditional marketing authorization so this will come okay so this is the what we have for the normal reversal agents this is pretty much new just published now there is
An antibody approach to inhibit techical or action so in patients who have tak tacular who bleed or need urgent surgery there’s now this antibody available but it’s unavailable it’s being studied to reverse the effect of techical or so this is platelet aggregation so basically this is high platelet aggregation if you give ty kragle or you end up here so you have
Low platelet aggregation if you give placebo you can see here platelet aggregation stays low and if you give the antibody platelet aggregation is normalized meaning high platelet aggregation so this is phase one 64 phase one health healthy volunteers but this is going into phase two now and now this is my last topic this is the rationale for a factor eleven anti
Inhibiting drug y factor eleven factor eleven is interesting because it is involved in in thrombus formation but not so much in hemostasis so idea is if you inhibit this factor you may have nice results in terms of clot prevention in terms of vte prevention but not as much bleeding event so this is the rationale for this so this is now showing that there was an
Antisense oligonucleotide showing that if you use this you have less patience with the vte and at the same time have less leavings than in aqsa parent and now the antibody was developed to have the same effect and this antibody against factor ten nila as against factor eleven is tested in the so called fox trot study which is i think completed or almost completed
The results will we will have the results pretty soon so this is testing a picc seban enoxaparin or the new drug in patients to prevent a venous thromboembolism so this will be out very soon okay now this is my last slide a very important study it is not the newest study but it’s important for you guys so it’s it’s looking for working hours and risk of divorce
Okay so this was a study in physicians physicians and there are striking differences in male and female physicians so when you look at this there’s no whatsoever effects of working hours in female physicians on divorce rate but if you look at the male’s the longer working hours clearly associated with less risk of divorce okay so guys if you work more your risk
Of being divorced is lower so if you don’t follow that and you work long sorry you were you do not work as long work-life balance you may be divorced that is not good because this is the child showing that this is investigating marital status and cardiovascular risk so not being married oh this file is not normal but anyway you should see here so if you’re not
Married your risk of cardiovascular death is higher and it’s even worse when you’re divorced if you’re divorced numerically your risk is even higher to die from cardiovascular cause than just not being married okay so anyway but if you survive and you’re not married you’re divorced there’s one thing you can do you should think of having a dog okay because dog
Ownership is protective force oh look at this this is a single household so divorced physicians okay so if you have a dog in this setting there’s less cardiovascular events and look at this cardiovascular mortality all cause mortality is significantly lower now if you have a dog and you have your little chihuahua on your couch watching tv and you talk to your dog
This is not what you should do because you need a hunting dog okay guys so you need a hunting dog so when you look at scent dogs pointing dogs and hunting dog breeds then your risk is low so consider this when not working long hours during the week so thank you very much
Transcribed from video
ACS / Antithrombotics – S. Wassmann By European Society of Cardiology
