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Ticagrelor in Patients with Prior Myocardial Infarction – PEGASUS-TIMI 54

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This interview with Dr. Dominick Angiolillo & Prof. Christoph Varenhorst discusses the efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label data.

Hello my name is dominic ng lila i’m a professor of medicine and interventional cardiologists at the university of florida and jacksonville we’re here at the esc live in barcelona and i’m joined by crystal baron hoffs associate professor of cardiology and interventional cardiologist from sweden so thanks for joining me thank you so a lot of interesting news

Here at the at the esc and in particular some new insights from the landmark pegasus trial so before we get into some of the details of this new information you just give me a quick overview of the pegasus trial yes the the pegasus team e54 trial was a trial testing long-term treatment with chicago together with aspirin in comparison tawny aspirin in patients

With recent mi within one to three years before randomization of the trial and the trial tested two doses of optic aguilera 60 milligram and the 90 milligram dose by daily and showed a 15 or 16 percent relative risk reduction of the primary endpoint over three years of cardiovascular death mi and stroke very good now this they come with a price of course yes it

Does and the trial also showed an increase in in timmy major bleeds fortunately there were no increase in fatal bleeds or intracranial hemorrhage that’s a good question now also within the trial i think it’s important to emphasize these were not just all patients who had an mi but there were some enrichment factors right these were patients who have to be above

A certain age above the age of 65 have died be ckd correct and multiple solutely so that is important it was a subset of mi patient at a high risk that’s very important to emphasize very good so um at this meeting there were some new insights from the trial the european medical agency as specifically requested that analysis be performed to try to identify the

Ideal population and to apply the sixty milligram dose which shelton was the winner yes trial yes that’s true we were to know from from the trial that the patients that seemed benefit the most was the patients were not the to distance mi those with an mi within two years and also those patients that did not have a long interruption of dual antipater treatment

For their initial mi so that didn’t have a cessation of more than one year so less than one year those seemed to be those patients with the greatest benefit and those were the question that the ma i also put us or or put the scientific community to show could there be benefit especially in this population and how does that look which ultimately it makes sense

In clinical practice right you would probably think about continuing a treatment or prolonging therapy in that specific patient population so great so what’s the data show well the data showed when when studying the sub ablation of patients with either a more recent mi up to two years or a discontent ation of less than one year of the pride you will agitated

Treatment there was relative risk reduction of the primary comp├ís event point in this population of cardiovascular death a mine stroke of around 20% an importantly cardiovascular mortality was reduced by 29% relatively over three years in this population and was it’s great information so essentially the analysis identified up let’s put this way a higher risk

Cohort if you will around 10,000 patients and so what we see could assist in theta with the overall trial but a greater magnitude of a benefit because of the type of population that we’re seeing so well we have this this new data we had the european label yes what does this mean for practices in europe in general and what does it mean for your practice i think

This this aids the the the practitioner when when choosing patients for prolonged treatment there’s always of course an offset with bleeding and reassuring from from from this analysis bleeding was was similar or lower to that of the main analysis but again with an increased risk of optima blades to me major bleeds but no increased risk of fatal bleeds and an

Intracranial hemorrhage and again this analysis was performed in sixty milligram dose and that is the dose that is approved but of course there’s always an offset with with bleeding’s when protecting patients of ischemic events and i think this this analysis helps a lot to select the patient populations where where we should and can consider a prolonged you’ll

Have to pay treatment with two kagura 60 milligrams well very good i mean i think you used the correct term and this label aids and helps the physician in the decision making because correctly as we mentioned before prolonging therapy beyond one year in the post and my patients not for all patients but we’re identifying the patients within a first of all higher

Risk category and then within that higher risk category this analysis teases thing out pretty well i would say the reduction cardiovascular mortality is something that we’re not so used to seeing in clinical trials so definitely something that in european practice having this dedicated label should be of great benefit well mantra just give me an example of a

Patient in your clinical practice where you would apply this new european label insight yeah i think it’s it’s it’s a great example of that patients that maybe don’t have the classical risk characteristics for stent related problem because we know from pegasus that we mainly effect spontaneous infarctions but i think these these patients exist we know that we

Have patients with multi vessel disease where there is still coronary disease present also standing after the period when we protected the stand and of course the patients with with comorbidities such as diabetes and and a reduction in in kidney function so that would be the classical patient in my clinic and maybe even more so for the jungle patients we’re

Calculating a precise tap to that score as the novel daffy guidelines would recommend would give us a hint at that we might have a favorable situation when it comes to long-term treatment regarding bleeding is also very good so it’s a kind of a combination between clinical judgment on one hand integrated by some scoring system and some help from from the label so kind

Of putting it all together we can make our decision with our patient well let me give you an example in my practice we’ve been using the sixty milligram now for more than a year we don’t have the label like in in europe it’s a little bit at the discretion of the physician and i can say that the label to a certain extent applies to what i do in my practice although

I think that at the end of the day from a true practical standpoint there’s a decision making process which is at one year and it’s there where you decide and you should down with the patient and have a conversation on whether to prolong or not so yeah it’s a little bit even more restrictive that’s what’s in the european label which looks at the discontinuation

Up to one year but if you look in another analysis from the pegasus trial if you look at the patients who had not discontinued or discontinued even within 30 days there’s a 27% relative risk reduction and so that’s kind of what i apply in my clinical practice so being here at the meeting and looking at this data and presenting it as well people have asked me

You know how does this european label apply to practice in the united states i think it’s very informal and as you mentioned it’s an aid for clinicians to keep in mind and showing the information including the mortality benefit is obviously a strike with the understanding that there’s still an increased risk of bleeding but as we say in clinical trials and when

We interpret results mortality trumps everything so the new guidelines were just released what do you think about the data from pegasus the new label change and the wording in the most recent guidelines yeah i think it’s happy to see that they match each other very well both the doc guidelines and also the de-stemming guidelines that were aligned for these two

Versions and and we can clearly see that that there is a willing from from the from the guyline orders to highlight exactly what you’re mentioning right now that we need to look into the individual patient we need to inform the patient and even more so for long term doubt involve the patient in the decision and i think the new guidelines they stress that to

The greater extent that it did before either by using risk scoring but also looking at the historical year we just had after an acs how did my patient tolerate the treatment and and how is the patient willing to to continue treatment after have given the information you just mentioned about the opportunity of our possibility of a mortality reduction of reducing

Spontaneous mis mainly what i think also what was great with the new guidelines is to see that for peroni treatment we need to stress those other factors apart from those mainly being coupled to to the intervention for the acs but because it’s not all about the stent anymore absolutely it’s all about it’s all about the patient and you know what i typically tell

My patients you have the best angiographic result by putting in a stent but i would say putting a stent is almost putting in a patch meaning a very small portion of the entire vasculature we’re dealing with a systemic disease and like what you mentioned that within the guidelines the wording is now more transparent it’s clear i mean we still have the same to be

Recommendation but they go a little bit more into specifics into the data from the pegasus trial specifying the 60 milligram b id and how would this can be preferred over other therapies which have not been the studied as in the pegasus like in the pegasus trial because there’s a classical question that comes up well if you’re using the sixty milligram the id

Can’t you just use capital first sample but that was not tested in the trials what i always tried to to explain and you also have a lot of experience with with pharmacodynamics and platelet function how is this sixty milligram work well i think when we saw the the date on the sixty milligram dose which has been pulled from the phone rather from the randomized

Trials we’re happy to see that this seems to be a more consistency although as compared with 90 milligrams the variability is somewhat higher but not at all to the extent them and that’s per capita goal and of course we don’t have the problem of genetic interaction as well and that is been proven from from plato sub studies and onwards so so from my point of view

From my clinical meeting in the patients that is of course reassuring on long-term how do you consider the bleeding risk and and the the opportunity of using proton pump inhibitors is that routine in your clinic yeah so it’s a good question you know in the past we used to use proton pump inhibitors routinely in a lot of our pci patients until a number of years

Ago there was a box warning for the drug interaction with with peter ghrelin and the new updated guidelines saying that he should not be used routinely in everybody but in more selected cases clearly class one if a patient had a bleeding event class two if the patients at high risk for bleeding but with regards to this sixty milligram long-term if i’m concerned

About bleeding probably not gonna try to protect it necessary with a ppi because a lot of these patients to a certain extent they’ve already proven themselves to be at low risk for bleeding by one year so if there’s an indication to be on a ppi then a lot it’s very different than for example a patient with atrial fibrillation and that may be on triple therapy

And and and well not that’s at least my my practice great very good well this was a great discussion um i think that time will tell how this this this data will be used in in in clinical practice a lot of great registries going on in europe and definitely in sweden nobody can beat you guys when it comes to performing registries collecting data and and looking

At clinical outcomes and so be very interesting to see how this all plays out in real world clinical practice but i think that the data we have our great asset to our patients important to help guidance in our clinical practice so thanks for having us and everybody thank you for joining us here from esc in barcelona and have a nice day have a nice day thank you

Transcribed from video
Ticagrelor in Patients with Prior Myocardial Infarction – PEGASUS-TIMI 54 By Radcliffe