00:01
So let's talk about
stroke prevention.
00:03
When I think about stroke prevention,
I divided into two buckets.
00:07
There is primary
stroke prevention,
which is treatment of individuals
with no history of stroke.
00:12
Those are patients who are at very
high risk for an ischemic event,
such as patients with atrial
fibrillation without a prior stroke.
00:20
And then there is secondary
stroke prevention.
00:22
This is treatment of individuals
who have already had a stroke
or a TIA and are at
risk for a future event.
00:29
What type of agents do
we use to prevent stroke
either for primary or
a secondary prevention?
Well, aspirin is one of the most important
and effective medicines that are used.
00:39
This is an antiplatelet
agent that prevents stroke.
00:44
Dipyridamole is another
agent that can be used
and sometimes it's
combined with aspirin
into a brand name
product called Aggrenox.
00:53
There are a number of
oral P2Y12 inhibitors,
clopidogrel, prasugrel,
or ticagrelor are three agents
that work through
inhibition of the P2Y12.
01:05
These are also
antiplatelet agents.
01:08
And then there are anticoagulants,
enoxaparin sodium or Lovenox
is a common anticoagulant
used in patients with stroke.
01:16
Coumadin or Warfarin is the
historical commonly used anticoagulant
that is used and requires
frequent monitoring
with many drug-drug
interactions.
01:25
And so often we use or
consider other agents nowadays.
01:30
And then there are the direct
oral antithrombin inhibitors,
which are called DOACs which
can be used to prevent stroke.
01:39
What are the mechanisms of
action of the antiplatelet agents
and how do we consider their use
for different types of stroke?
When we think about stroke,
there are Cardioembolic strokes are
those that come from hypercoagulability
and that's one group.
01:53
There are thrombotic or lacunar
strokes, and that's a second group.
01:57
And then other causes of stroke
where we may need to consider
different interventions.
02:00
And I think those three
categories are helpful
to understanding the types of interventions
we would consider in these patients.
02:07
For patients with a
Cardioembolic stroke
or evidence of
hypercoagulability.
02:11
For those patients,
anticoagulation is indicated
and initiated early and
continued after the stroke,
except in patients
with large stroke,
where there are a
significant hemorrhage risk,
where the initiative
anticoagulation is delayed
until patients are beyond
that risk of bleeding.
02:28
For patients with thrombotic
strokes or lacunar strokes,
antiplatelet therapy is
the treatment of choice.
02:34
We consider aspirin or those oral
P2Y12 inhibitors like clopidogrel.
02:40
And then there are other causes of stroke
that may require different interventions.
02:44
Watershed strokes are strokes
that occur in those distributions.
02:48
Those watershed distributions
in between vascular territories,
such as the MCA/ACA watershed
area or MCA/PCA watershed areas.
02:58
Those strokes occur from
reduced perfusion to the brain,
and IV fluids or reduction
of antihypertensives
may be needed to manage
stroke risk in those patients.
03:09
In all patients
presenting with stroke,
we need to consider risk
factor modification.
03:15
So let's talk about the mechanisms of
action of some of the antiplatelet agents
that we use for
prevention of stroke.
03:23
First, we have the
oral P2Y12 inhibitors,
clopidogrel,
prasugrel and ticagrelor.
03:30
Next we can think about
aspirin is a second category
with a different mechanism of
action and then there's dipyridamole
which also has a different
mechanism of action.
03:39
The oral P2Y12 inhibitors
block ADP receptors
and this really contributes
to their reduction
in platelet activation
and aggregation.
03:48
Aspirin on the other hand
inhibits cyclooxygenase or COX
and thromboxane A2 and that really
contributes to its inhibition
of platelet activation
and aggregation.
04:00
Dipyridamole has a
couple of actions.
04:02
It increases plasma adenosine and
increases platelet phosphodiesterase
both of which contribute to reduction
in platelet activation and aggregation.
04:12
So the mechanism is
different for each of these
antiplatelet agents
or classes of agents.
04:17
But the end result is inhibition
of platelet activation.
04:20
The platelets
become less sticky,
and there's less aggregation of
platelets to contribute to clotting.
04:25
And both of those things contribute
to a reduction in stroke risk.
04:31
When we think about the
mechanisms of action
and how that works in the
setting of an acute stroke,
a stroke it results
from plaque rupture,
and there's activation of platelets
and aggregation of platelets
contributing to a thrombus or a clot that
reduces perfusion to a part of the brain.
04:46
Some of the things that happen after that
plaque rupture is increasing thromboxane A2
and that's really
what aspirin does.
04:52
It inhibits that
TXA2 production.
04:56
ADP is also released and there's an
increase in ADP within the blood vessels
and the oral P2Y12 inhibitors as well
as to some degree that dipyridamole
reduce ATP generation and circulation
around that area of plaque rupture.
05:12
There's activation of
GPIIb/IIIa receptors.
05:16
And there are a number of
GPIIb/IIIa freeway antagonists
that are also being studied and can be
used in selected situations for patient
with acute stroke or with
myocardial infarction.
05:27
And the end result is platelet
aggregation with thrombus formation
and the goal of all of these
agents is to prevent that process.
05:35
Let's look at a comparison of some
of the various antiplatelet agents.
05:39
These are common medicines used in
the secondary prevention of stroke.
05:43
And it is helpful to
understand their advantages,
their disadvantages, and then some
unique features of each of those agents.
05:50
Aspirin is an antiplatelet agent
that is used very frequently
because it's inexpensive and
we have a long experience
and good safety
data on this agent.
06:00
Some disadvantages is in selected
patients that can have limited efficacy,
not every patient
responds to aspirin.
06:06
And we do know that there are
aspirin responders and non-responders
and in those non-responders,
alternative agents may be needed.
06:14
It can irritate the GI
tract and cause it gastritis
and so patients may present
with gastrointestinal symptoms.
06:21
And then we worry about this
possibility of resistant.
06:24
But it is often the first
choice in stroke prevention
both in the primary prevention and
secondary prevention of stroke.
06:33
Aspirin and dipyridamole in some studies
can be more effective than aspirin alone.
06:38
We can see a number of of similar and
different side effects to aspirin alone,
including headache and
gastrointestinal symptoms,
and it requires twice daily dosing
which may be difficult in many patients.
06:50
And then we have the oral P2Y12
inhibitors like clopidogrel,
prasugrel and ticagrelor.
06:57
They can be more effective than
aspirin in a number of studies
and effective in
combination with aspirin.
07:02
Aspirin and clopidogrel is commonly
used for dual antiplatelet therapy,
which can be more effective
than either monotherapy alone.
07:11
Side effects that we can
see with these include rash,
they can be more expensive and response
also can be variable in selected patients.
07:23
And then we have the category
of dual antiplatelet therapy,
aspirin plus clopidogrel.
07:28
This is a potent
combination of agents
that is considered in patients
with minor stroke or TIA.
07:34
There is an increased risk of bleeding
both CNS and systemic bleeding.
07:38
And so dual antiplatelet therapy is
really considered early after the stroke
within the first 30 to 90
days that peak period of
where patients are at
risk for recurrent stroke.
07:48
And then patients are
dosed reduced or reduced
to typically aspirin
monotherapy alone.
07:54
And this is used as you see here
in patients with TIA or mild stroke
and that's measured by the NIH Stroke
Scale, a score of less than or equal to 5
and in mild stroke with significant
extracranial vascular disease.
08:08
And then lastly,
there is an agent cilostazol.
08:11
This is a phosphodiesterase
inhibitor, it's used very rarely
but you'll see it
sometimes used for patients
who have failed all of the
other agents we've talked about.
08:19
Patients who have had
a stroke on aspirin
and clopidogrel or the combination
of dual antiplatelet therapy.
08:26
This agent can be more effective
than either agent alone,
it's an antiplatelet
and vasodilator agent.
08:32
We can see headache and
gastrointestinal symptoms
and it's not FDA
approved for stroke.
08:37
But in some cases
considered off label
for patients who have been failed
or refractory to other agents.