When to start anticoagulation after hemorrhagic stroke
Anticoagulation after acute stroke – when/ how to start
thank you very much miss Opoku it's a
great pleasure to be here and I'm very
happy that you just pointed to the very
important question I'm trying to answer
to you now because I only started
talking on heparin so my task was to say
something about the when and how first
of all here my disclosures so the most
important here of course that I'm a
neurologist first thing I asked myself
and I would quickly go through it so
when talking about the how and when what
is the evidence at all you all know that
we're talking about acute ischemic
stroke patients now that most of the
studies were done in patients with a sin
not necessary in patients with stroke so
what is the evidence it's it's
tremendous because we go back to 1993
just very quickly maybe a time point
when some of you weren't born yet or
haven't been have not been in school yet
and although that time the AF sorry
there was a tremendous effect of of
warfarin and perceiver was this great
reduction in new Ambala strokes of
recurrence in these stroke patients we
are talking about in the subgroup
patients so what's the evidence from the
dog trials all of these child included
patients who already he also had a
stroke and there sounded to suggest that
all the dogs also reduce the risk of
recurrence impacted had a stroke so what
is all the discussion about then the
when and how well it appears very
interesting or it's very interesting
that most of these trials on the dogs
did not exclude include that had very
recent stroke the rely study did not
include patient was in 14 days
rocket AF trial did not include patients
that had a stroke within the last 30
days the era's tosyl study did not
include patients who had a stroke was in
lost seven days and so on and even the
ef-2 study had the majority of the
patients included within 14 days but
were allowed to include patients up to
90 days
second row shelf is a number of patients
with jokes that were included in the
trials so for some reasons they were
very worried about including patients at
a very early phase in the very early
phase of acute stroke so this concern of
course is as mentioned before because
early initiation may accept or
exacerbate or cause have a
transformation or even parenchymal
hemorrhage something we are very afraid
of but what do we know about early
initiation is this a relevant concern we
have it's always two sides of the coin
isn't it one side of the coin earlier
which is assumed to be very high data
dating back to the 80s suggesting that a
patient had a stroke has a very high
risk to have a recurrence in the early
days up to 1% per day and on the other
side the fear to cause regular
hemorrhage or hemorrhagic transformation
and we know that this would very much
impair the prognosis of our stroke
patients there's only one randomized
controlled trial which gives the stage
of on very early initiation only this
very small study on not not yet two
hundred strokes patients was a very
small stroke you all know the NHS S
which is the score for stroke severity
too is very little not very much
impaired just a very small stroke and
the in fact volumes are very small to
they started in the media on day two and
their goal was to see how many new
events there would be on MRIs so no
clinical outcome just circuit marker
they compared rivaroxaban and warfarin
and did not find difference between
these two neither a new DWI lesion so
it's a good market for new stroke nor
for new bleeding on t to store images of
the MRI so in this cohort of patients
with stroke small straw
not severely impaired it seemed to be
safe from the part of you that there was
no difference between rivaroxaban and
warfarin or other data we have is data
of cohorts of prospective follow-up
studies and we do have and this actually
point to the question which we just had
we do have data on parental articulation
or Hedren and this data from this media
analysis which does not include of
course those concepts from 2007 did they
tell us that there was not really a lot
of data suggestions at which that we
should give heparins rather it tended
that there was no advantage at all to
start with heparins and when we look at
the Y we see again there's a mm yes
there heparins the parental interference
did reduce recurrence was a significant
odds ratio are not nearly nearly
significant or three with a number
needed to treat about 50 but on the
other ha on the other side it did cause
bleeding with a significant odds ratio
and a nominee division harm of 55 so
that was reason you know the the benefit
you bought was paid by the disadvantage
of the bleeding's so nearly all the
guidance a early administration of
parental or intercalation in the DOS
calling relevant blood-thinning not the
dose of preventing deep vein thrombosis
is not supported because the net
clinical benefit will be set off by the
bleeding sea cause in relation to the
reduction in recurrence you gain so this
data was about heparin and warfarin what
we know was a direct oral integrant so
this is again data on the subgroup of
the post stroke patients we all fear
bleeding of course this is a slider
always get a Oh from the audience when
it shows this little small
thank you okay I will fear of course
intracranial bleeding so so what did the
data show the data showed the New
Orleans are nearly all safe or all the
doses less severe bleeding less via
intracranial bleeding so this would be
an argument and that we are better off
as a direct oral anticoagulants and
might start earlier so this would be an
argument that those as opposed to
heparin and this assumption is always
also supported by some observational
studies we have like this notice this
array from Japan or the ref no work
study which also low inter Canyon
bleeding risk with door works including
hemorrhagic transformation if you start
early
this again is registered data supporting
the fact that we should not give low
molecular weight heparin and the data
now includes also darts the paper or the
the draft was on patients that did not
receive torques because they were not on
the market so basically supporting the
Assumption if the start was low hi Jose
this is not good for the patient as you
see that low weight heparins those cause
more ischemic events or do not prevent
more ischemic events as a yellow bar is
higher than the green bar and do not and
also cause more hemorrhages so again
early administration of habits not
supported bridging is not supported so
wide of timing measure the question was
about the wind so what do we know about
the timing then okay we know that in the
large Charles there were very few
patients that were included before day
14 does a few be day 14 will see a big
smart study so why is that obviously
because
early start of orientation is a
predictor of pure ankara hemorrhage
although the data could be questioned
because most analysis do not reach
statistical significance and because we
already mentioned that before parental
hemorrhage is a very strong predictor
for male outcome so what do we know
about the right time point is this
analysis from stroke 2015 again registry
data no control data where they try to
pick the best time span with both the
lowest return rate and the lowest energy
age and in this analysis just in multi
regression analysis it was between days
5 and 13 that the patients were best off
so this is an argument just from
registry data to start earlier than day
14 but not only the day four to three
again this is mainly patients with
warfarin just to stress that of course
we have a heterogeneous group of
different drugs and this is the analysis
supporting or suggestion that early
start
but not too early it would be the best
timing to go on with a regulation what
does the guidelines say we do have
guidelines and the guidelines actually
give us hints so ever answer
neurologists of course first stroke
minds and they say start at a four in
March job it's more in fact started day
seven and moderate stroke was medium in
fact and started a fourteen and severe
stroke with lot in force they also say
bottom line based on observational study
results reading therapy that was the
data I just showed you is not supported
prior to our integration must not be
used in patients AF and ischemic stroke
strong evidence or strong
sentence so here they make the point
it's not only time it's also about the
size or was a very interesting question
to talk about size and they say small
medium large they do not tell us what
small medium and large actually means
that just says small medium and large
but they do not give us any finished I'm
a bit remote control I'm sorry so what
does the ecological unsafe see
cardiology guidelines basically say the
same thing they start straightaway on
the left if you have a mild neurological
deficit small strokes or other few days
if you have a moderate or if you have a
moderate deficit Scott after six to
eight days with the severe deficit start
after twelve to fourteen eight but they
somehow introduce an extra point to be
here and to have more data to to build
on
they tell us if you have a moderate or
severe deficit better make a second
imaging and look at the second image and
look whether there's any change to the
in fact so same recommendation as the
neurology stroke recommendations more or
less one three six twelve so you double
the number so to say but very
interesting this recommendation made in
the 2018 you accommodations based on the
2013 recommendations they are basically
the same nearly the same and those based
on the warfarin data so that did not
somehow tell us that now they recommend
something on dogs which was basically
derived from it from a friend or
although we know that the drugs are
different again the given that it was
not a very good definition on what minor
moderate or severe means so they
emphasize and this is the only guideline
that recommends repeat imaging so the
size matter
yes size does matter
large reasons do predict prank or
hemorrhage and large
also do predict parenteral hemorrhage
and stroke patients with AF and yes it
does we do not want that this happens a
patient was a lot right in sixth row
which has a Frank remembered
so what will the future bring of the
future will bring us for more trials one
European one British one Swedish and one
Texan trial that all started with
different assumptions and different sets
to compare early and late initiation so
we will have more data to answer this
question but I cannot give any
information on these Charles apart from
that they are actually happening at this
moment so what the when difficult
question is there is only few data
regarding the timing of course very
simple answer it's a risk-benefit ratio
there's two fighters point and we have
to weigh benefits and risks as far as
the works are concerned it seems
reasonable safe to start within 14 days
and not later
although the trials did not include
patients for most of the charts include
patients earlier than 14 days stroke
size may help but it is it's a very
individual judgement we do not have a
definition in terms of milliliters or in
terms of what actually large means the
trials actually have so the Elantra has
a suggestion where to find the cut-offs
and we might just stick to the
guidelines and choose our one three six
twelve algorithm although they did not
differentiate between warfarin and dogs
and how well there's strong evidence not
to bridge actually you're going for dogs
because they have a very similar
half-life anyway so there's no advantage
in terms of pharmacodynamics to first
start with heparin and then start to
dogs
um neurologists actually start with
aspirin even if you have atrial
fibrillation and then switch to dogs
because there's all this data about the
bad-bad heparin and I hope that very
much in the future we will have new data
to answer this very interesting question
one early initiation thank you very much
for your attention
[Applause]
