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so d. m. i found actually d. set picture quite quite
inspiring systems fate what an artist's uh feels uh
uh when uh she has a a a vein troubles the deep thing troubles is
and uh and and you see the the the degree of saw friends and uh uh especially
uh uh in the treatment of this kind of fumble this is a very standardise and
very advanced uh something similar happens in the in
the portal vein of jesus and despotic area
but we we don't know exactly what's the consequence are in this in this area
and we are absolutely not advanced in terms of standardisation of treatment and even
less uh in terms of onto cooperation so what i wanted to
a good tool would you worked three points the mechanism veterans of
a new a class of rocks the affects of these uh
direct alright i've ah to quite blunt especially in patients presenting with
a chronic advance lever disease and uh i'm finally some
words about uh the indication if there is one about monitoring
and uh which dog is good for which patients
we have our uh free directing beaters or factor twenty we have one any better off from being
and the acting the final part of the cascade indy
are currently i'm used for the prevention of stroke
for the treatment of venus from where embolism for the prevention of a trim waist one is after
me or heap are purposely not thing to do would portal vein proposes the real novelty
is that uh tends to set a a degree of a of a safety is that we
can uh antagonists this we can do with with a a ten a uh um yeah
to um uh antidote switches uh and excellent we can utilise that we get front with an antibody
and uh in uh probably the next month we we have a a
a new one which is syrup around talk which is a
a general uh an antidote for orange quadrants that we are uh
currently uh using of course not for vitamin k. antagonist
so the evidence that uh these trucks are good calms for or
from a big registration studies use here dear
dear dear uh it being housings of
patience and what what it is interesting is that in terms of uh
of us for core systemic timberlake events compared to vitamin
k. antagonist when you want to quadrants are better
okay in terms of building a the pieces
to this is to be differentiated because yeah you see that
uh there are two oh uh drunks which are pick
seven and it took someone which are clearly better so less bleeding then on to vitamin k. into drugs
that we get from the river oaks of and where this evidence is not based
clear so if we um focus on a efficacy and
safety outcomes we can clearly see that's a docks
are better in terms of a more logic stroke they are better
in terms of uh inter crying out hemorrhage but interestingly
uh and this is relevant to particular eleven for
us as far as gastrointestinal bleeding is concerned
probably dogs are more dangerous than uh on t. vitamin k.
uh these are data from a registration study what to use uh in in the
real word in the real word you see that if we uh compare
seventy thousand two more than fifty thousand patients treated with dogs or
we'd harder and requirements in terms of g. i. bleeding
there is no difference so we can conclude okay there is no problem however if we have a closer look
uh to this data we see that the reading crystals of major j. believing
that are associated with that be that front plus twenty seven or
revoke seven plus forty percent but not for the other ones there are
some risk groups which are patients over for a seventy five
patients presenting liver dysfunction uh impaired the party functional we've come
back to this end concomitant use often to brackets
and finally uh h. two receptor antagonists or p. p.
i. appears to be protective against uh against building
and if we compare uh uh relate to each other the
different uh dogs in terms of risk of gastrointestinal bleeding
you see that uh and i'm not going to details but
compared to the other um docks optics upon seems
to be better than the be the trend and the bigger trend seems to be better than remarks about
so taking together this uh data shows us that uh that be that
trend and vivid rocks upon in terms also major baiting overall
are the same as vitamin k. antagonist while at big seven hundred and that talks about her better
major ga bleeding is uh is higher would that be that front
ends weaver oxygen but not too with with the other two
and it's major inter cranial buildings is lower with all the locks compared
which is a a and t. vitamin k. uh um
medications once again in the real word in the
state of more than forty thousand patients uh
this is our confirming that a a major bleeding events uh ochre less
frequently in a in a the locks than in a war firming
hear the difference is not really a significant inter cranial
bleeding of course less uh but you see that
yeah it should be eating uh uh at least for
uh the b. that final course uh more frequently
so while it occurs where uh those it's does it do so
in the upper g. i. tract it's a a pack teach also disease in
the lord your track to see that uh the vertical are um
the article or bleeding but interestingly if you look at uh the
percentage of patients who has to have to be osprey televised uh as you can see
that this percent is is a fifty percent impatient with docks a while it
is a a much higher in patients with conti vitamin k. and also the duration
of uh or speech energy hospital decision is screw shorter in patients treated with
a dog so clearly a an advantage these study is a excluded as the vast
majority of the other studies is excluded patients with zeros is so we have
to look into the studies to find out patients with zeros disease or a survey
uh all of a a gastrointestinal bleeding after endoscopy each interventions and uh
uh we see that in general uh the incidence of
bleeding is higher in patients treated weights or suffering
compared with docks this is not a statistically significant but it's
always it's always the saying trends and uh if we
look closer to an indication which we found we find
that uh endoscopy should various allegation is also included
meaning that she or a a a sorority patients must be included
and and and treated with with the uh with dogs disease uh
fifty versus a a fifty four and you see that uh
there is here also a a march of uh uh security
if you want to but this is not a significant
but this is something that fits that happens so the frequent situation is uh that we use
dogs uh when you we assume that the reason only the disease for a very common
uh conditions that i'm not related to advance chronic liver disease and this is a rare situation
where we know that our patients are a um a lever sick and we
treat conditions that are associated with this disease support having trouble this arbitrary
of course patients with advanced liver disease can also be treated in these
in these indications but in the studies this patients have been excluded
what are the effects of the works uh in these patients we
have to uh scenarios on the left side you see the
changes that we observe in patients with stumbles is primary most
places is disturbed cooperation is disturbed fibre analysis is disturbed
we have to take into account this and on the other hand former co kinetic
um uh situations are different and i'm i'm going to show you an example
and a farmer coding on each uh aspects as also
different because there wasn't a an increased or did
might be an increase plus my plasma level of this uh drugs but data are very um
very uh controversial you see here the levels of
a river rock seven impatient had to subject
patient with mild or moderate the political impairment meaning child a in child you and you
see as expected that's the levels of a a plus money the rocks about our higher if
the lever is stick in that action of a uni beating tiny is a um
is more is higher and it probably the pro probing time is higher here so expected for iraq's about
for a for a box upon we have the country you see you see
here that there is no difference in concentration but uh if uh
if you see uh the data in moderate departing payment you see that
uh in the head the subject uh uh the the the level
orthodox someone is higher dan in a a lever such a subject so we don't know exactly what
the mechanism uh are but we we we we cannot conclude uh with with generally that uh
zero to patients have higher level of these drops another point of course is drug
induced liver injury it is expected enough to one percent of the patients
it's less frequent than with low will occur are way temperance or vitamin k. antagonists it's
more able to sell were then course static injury and it is more frequent
with river rocks about dan would that be that front or uh peaks
which is relevant what is relevant for us is that uh we
are using some some dry conservative patients in when we
decide to want to cooperate we have to uh draw attention to the fact that especially with the big upfront
and in some cases wait it talks about we have to call c. there i read option
when we use a beta blockers when we use stay things and when we use um
a thankless boring or probably most in our transplanted patients
one of course the in only only really really uh zero to but
keep in mind that uh uh this can be an issue
in another issue can be lever injury you see that's a d. u. um attitude should be different
that electron is the lesser a safe drought in this uh uh context you see that
uh in levels of cutting the clearance less than a a fifty meters
per minutes we should decrees any level it's a on of less
than thirty meters of uh uh per minutes you have to decrease
the those two fifty percent whichever also wanna know doc seven
and also here to to fifty percent and consider that basically in patients with a crafting enough
not threatening clearance of less than than a fifteen
it's basically a no go for four blocks
the data uh about the safety as if it and efficacy
patients with it's uh s. roses are very rare
you see here all the studies that are available low number of patients a little uh or
short a duration of a followup major breaking occurring
in a proportion that he's actually uh
in the same range and is the proportion observed in anti vitamin k. a.
or a low wicker way to point but remember that these studies a
retrospective and then not have not been designed for for a process this and
what what is of course a problem for us is that the
the the proportion of security patients child see is uh
zeroing the majority of the study and fifteen percent only only in one in one study so
uh did the data uh showing that major bleeding uh
easel covering more or less uh with the
same frequency as a as a the other on
squadrons must be taking very very cautiously
um it is interesting to see that uh in a in the context of truth in a strong one policeman uh
in patients presenting with uh elevated serum i mean the
try a trans i mean is is um docks
our our uh um i think the study where um prescribed much more frequently
then uh uh on t. vitamin k. e. uh medications it's not clear
why but uh it's also interesting to see that in intensive care
uh uh the treatment of uh i'm actually things from what
is is that really really uh done with dogs
in contrast emergency care station this is the most the use of the
drug probably because uh uh with dogs you reach a a very
rapidly uh uh the the right speech a plasma levels and uh
this is the distribution of the use of our uh products
a deluxe entities probably what we also do does more uh more or less at fifty percent to rocks
about forty percent the big seven weeks upon and uh a bit uh docks upon and the bigotry
in the there are two other considerations that i would like just to mention and it is that the locks
in not all basically uh it can be used but they can cut a accounts that there is
a a a large volume of distribution and basically what
you should consider is that in patients with a
b. m. my of more than forty or more than one hundred and twenty children body weight
you should not use a a dogs uh and gore
other for a vitamin k. antagonists and uh
this is a concern was all in patients who are a little weight
impatience of less than sixty kilograms you should reduce
uh those at least for a big seven and the docks about but there are no recommendations were all fisher recommendation in
this area but consider that a frequently uh see what the
patients presents a a sock opinion and this should be
uh uh taking into account the locks may be good for security patients
because they have some and if i brought each uh um
action you see that they contributes in an animal model
to uh improve into t. i. dysfunction they are associated with last fibrosis as a
see that uh by quantification of us i'll have a small monsieur acting
ends they can lower puerto pressure although this is a a um
this uh use uh mm it's in statistically
significant but it's it's uh uh uh
only only point four percent and this is not a good uh only for
the lever the antibiotic effect is uh uh was observed on carpet fibres
results of sort of i don't go into details up except on is uh
also in a beating fibrosis in pulmonary fibre blessed in that we
get found a decreases in you know in v. form or the five
boroughs is of the longs in people so it it appears
to be a general uh and if i brought each effect and uh
i'm going to a close my presentation with the last part which
is uh important because you cannot money toward your d. d. d. the
efficacy of the tree to me docks however you should know
that uh especially locks upon is increasing uh do here in our uh
value of your patients but you can use the n. r. as as up
as i'm a marker all funky cooperation in that case and that that
electron is prolonged in the g. d. yeah a p. t. t.
so uh i just taking two into account decent this is another a way of seeing these things you see
that uh a pity and the input from in time are increased but uh you see that uh
pro and speak levels are overlapping here for that you
get from any particular for a pick someone so
if you measure the the the the plasma level of the straps you cannot
the say where where you are if you are in a in a in a a
in an area where you are um therapeutic rather choppy twentieth efficient or or not
and uh you see again the very larger interval of concentration
in a in a in class model for all the for
a dogs and you see here that when you know
uh the concentration is increasing the un t. ten a action
is uh is uh not not morning or so
you do the she messages that you can you you
cannot use plasma levels to uh evaluate the
efficacy so basically the recommendation that we have for the
use of dogs anybody's are that you should evaluate
your function test before starting and consider that there are practically no data in shied see patients
you should monitor liver function during the treatment especially the elderly patients or patients taking other um
people to talk such a drunk forty you should adapt the doors according to the renal function
and you know that uh security patients are have a very variable a kidney function
and consider stop docks in case of a step of uh was position for drug related it but the
toxicity tried a is a is a green area
a caution is needed for child be patients
and for child see patients um caution is is is recommended
uh i think we very rarely treat these patients and if we do so then
that we limit it's at a c. ten or or or or eleven
uh and this is my i think almost three seconds last slide how do you select
the right the ox considering the patients profile uh when the release euros is
is the reason i risk of gastrointestinal bleeding in this
does not include uh viruses that includes uh
a risk of bleeding in vices which is the dimension
and the right size but not viruses percent uh
it's better to use a a big seven or the bigots running reduced those if there is a
high risk of general bleeding then saying kings but you can use all the docks upon
if you have a uh an advanced liver disease child be then a core or
maybe it's good to avoid river rock seven for a a a decrees uh in a renal function
yes then uh fifty meters per minutes curtain clearance then you should
decrease or consider decreasing the dot's en it's uh if
for the patients is not fully compliant or once only one uh p. per day then the
river oaks upon or it looks upon should be should be selected so into close
uh i would like to to to conclude by saying that currently available data
so just the dogs are safe and effective uh in the presence of mind
to more the right advance chronic liver disease so opt to try it
b. b. nine or c. ten data are needed in stage see patients
in addition to liver function we i figured right interaction asian be
yeah my should be considered before starting this treatment docks may
have also on to fibre optic treatment so they could be indicated
in the um uh five brodie diseases including zeros is
in serum levels are not sufficient for monitoring
our soap here and i thank you for your attention
hannah lisa mm thank you very much and uh it's really a difficult topic at the end because
i always ask myself what to do when we have a patient
with a child c. is on the way to respond transplantation
bean develop those are nice for the winter mosey beneath not
complete that we want to preserve the papacy or the
a conference and you because you you need to receive a transplant then
we need to treat then we cannot use the works then um
mostly this patient have a good reason features you so they
are not ideal candidate anyway what do you do personally
it's it's it's a very complex situation might personalised experience but i think we
can share its or maybe blowing i dunno bits this safest order
easiest to to to to use triage are a little more like are
we temperance uh if you have a ah unacceptable kidney function
uh i'm speaking about really zero to patients the the patients on
the least uh with uh because of h. c. c.
are different they can be use with dogs they can be treated with dogs but they re us robotics are are
are really difficult and uh i think personally i tend to to switch to um
to look for what happens but they have to to to to inject it
and uh and this is not that easy and you have a two c.
d.'s patients very frequently because if they uh develop it but we'll syndrome
or any kind of like you have have as we have seen this morning this is a this is a major problem because then you should
go for for a non fraction it it forms a whimpering and this is this is
this is complicated so my personal preference is a fax
repairing or clicks on is that ordering your
more freedom to tie traded those those with low manipulates freezes this page and often have a
if not to mention the low platelet counts soul how how
lowell you'll there to goal with uh and columns because most of
these at least anybody we cannot prescribe when you want
to call warrants a bit direct and problems for a portal
in trouble just because that existed only for uh
prevention most rock and for our and we'll probably embolism so the second question is
in case use it for both of interim balls is do you think that this
same those is the recommended because really the the others are life threatening conditions
portal interim was used as a that was said not always is a life threatening condition um so
it might not even be directly their functions so it is really needed that would give the
full dawes or we might maybe after one mansell words will be those that the nobody no the
present so but if you have your personal opinion it would be nice to hear it
mm that i that was mentioning it and that has been always be
that paschal from boxes near the call for and that then
then what we do all is a trial of low weight a
plane and if he doesn't work we go for tapes
that that's what it back to you and uh
to complete a form thing from e. d. but really if it's lacking in pregnancy we
don't have data so for the history and the companions this don't you see
well it ended with vitamin k. it's always the question it favourite so let's
say in the past week like the switch to the l. x.
it it the data is it clear what i bought probably because it wasn't like
it's coming on the market or a cox our dates on the market
uh the problem it let me know this disturbing you
can smash and that makes it more complicated in
in levers in in in surrogate patients i'll try that c. i. c. patients had to say
i'm a strong believer in that part but i mean we say
single pill for all patients except for the extremities i'm in body weight
and just for us real something we most frankly see as a as a country indication that
you know what it would be yeah at that site apology patients so we had this this this
is not a with with that out with chemotherapy i bought that even with vitamin k.
i mean that that thing is like family well kinetic so that it's like a little more
like away hap right so so even after intake and you have a complication i mean
four two forty six hours late at the half life is already
gone so all the discussions on and you got someone is
bullying and you don't even like to too late so he
you have even with vitamin k. antagonistic allow that matches
and and he i mean until the patient in the hospital have like ten what gone and you're dealing
with something we all know follicle wait happens and we don't just discussed that inside the as well
so so my fault it's it's in favour wrap up the problem is ah
there are no they they nail recommendation for the sake of
the industry and and ah e. for legal issue
or any other questions
i'd together with the patient to use dog and we have we have patient
mean don't even mean waiting list on the drawn transplantation these very important
to discuss with patient the pros and cons and to have a return
documentation stating that the patient wants to go and accept the reason
and to discuss interdisciplinary also with the code except the weight is because for instance
um is this your reduced at that issue with a patient that was
on the rocks one and it was called the unexpectedly for transplant
and then they could not antagonist so that's why now for these
very specific cases we do not longer use them so it's
i think it's very important to be very open and close by and go to the discussion does unknown an unknown yeah yeah
o. e. k. o. e. c. d. how flat it's so short and we don't think about well michael way
hap right so so even in tight see personally i would vote for deluxe except the special situations
as a few relation and pulmonary embolism you might stop if you'd was the first occurrence
in the the situation as disappeared if you the second instance you goal long life
if you use a for portables rumbles which is your time you knew how long should be should be taking
yeah and the calculation because for instance for oracle wait a plane
initially we tended to so expand it a one to two months after the disappearance of the
traumas but we had a thirty four percent of recorders so now we have we baiting
how long whether you this is the yeah i don't have any as
but you know that's i was it on to the any answer but my
attitude or how well you don't monitor them soul you save a
physician consultations u. c. v. in our measurements every week so in the
end i'm i don't know if it is really more expensive but
okay okay you know right
want to come to your to your question i think that uh if you identify
risk factor for puerto having troubles isn't is risk factor is to present
as you mentioned so a trouble free yeah oh or or or
or or whatever the including in my opinions you roses
is that on the field factor then uh probably to make sense to continue
if you have a local factor that is eliminated or issue have a a point of
income poses due to c. m. v. infection it should seem infection or or
or something that you can you can see and you can demonstrate that it's over the risk is over
then my opinion it's justified to stop a treat and but in zeros
this if we accept the two roses approach for multi condition
then i would tends to continue although it's true that we have
for this to seventy percent of cases of spontaneous resolution
of composes which would not justify articulation
i think that the the more importation is paradoxically to see whether
and the well once can improve zeros is it they improved because we will
use them all over and when we land in every single situation
if this is not the case they need a little bit of to to gonna
catch say so it has to have an impact and probably orgies and
and uh the the the the studies of a recovery like that was in these as i think
has not been depicted it typically has been said that many more people will do the same
as the the the gunfire with the night but it's it's not and so um
we need such information on a block it's occupations you always good with opera genders could be
i don't do it's a always i. e.
yeah i get that workers is in the home
because the corporations states
what it did to your study would factor seven demonstrate that if you change corporation you don't improve anything
in terms of of of outcome of bleeding right
then no we we should then we should
yeah and if we have if you have viruses are introduced me to brokers in then you want to go with it
there are various questions
i just increase the flow dramatically i do create up it imposes but
the change in the speed the plough with but that locus about probably to circle
then you have other effects of that will that be a a farewell and it'll be
the product of like ox right you can you can modify the things i
okay i think each we stop here thank you very much to all i
would like to say two things the first one is that uh
we have the we have the opera which is the most important thing up arrow and it occasional
uh events are supported by the industry so thank you very much to uh your support we
could not do this if uh you were not here
so thank you very much um for the
people who need star here um participation so uh
uh documents so just take one copy
thank you very much for your for your contribution rupert to see patients so you will

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