Safety of Triple Antiplatelet Therapy - cardioegypt2011
Safety of Triple Antiplatelet Therapy - cardioegypt2011
Safety of Triple Antiplatelet Therapy - cardioegypt2011
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SAFETY OF TRIPLE<br />
ANTI-PLATELET THERAPY<br />
R&M Solutions<br />
Pr<strong>of</strong>. Ahmed Zaghloul Darwish<br />
M.D , FACC, FESC<br />
www.rmsolutions.net
Platelet Activation Mechanisms<br />
Thrombin<br />
generation<br />
Coagulation<br />
Thrombin<br />
Shape<br />
change<br />
PAR1<br />
Thromboxane<br />
A 2<br />
PAR4<br />
TPa<br />
Alpha<br />
granule<br />
Coagulation factors<br />
Inflammatory mediators<br />
5HT<br />
Collagen<br />
ASPIRIN<br />
x<br />
GPVI<br />
Storey RF. Curr Pharm Des. 2006;12:1255-59.<br />
5HT 2A<br />
PLATELET<br />
ACTIVATION<br />
ADP<br />
P2Y 1<br />
ATP<br />
P2X 1<br />
a IIb<br />
b 3<br />
a IIb<br />
b 3<br />
Fibrinogen<br />
5HT<br />
ADP<br />
ATP<br />
Dense<br />
granule<br />
Amplification<br />
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x<br />
x<br />
P2Y 12<br />
Aggregation<br />
a IIb<br />
b 3<br />
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TICLOPIDINE<br />
CLOPIDOGREL<br />
PRASUGREL<br />
ACTIVE<br />
METABOLITE<br />
GP IIb/IIIa ANTAGONISTS<br />
AZD6140<br />
CANGRELOR<br />
Platelet Activation
Introduction<br />
<strong>Antiplatelet</strong> therapy is the mainstay <strong>of</strong><br />
therapy in many settings in cardiology, namely<br />
percutaneous coronary interventions (PCI) and<br />
acute coronary syndromes (ACS).<br />
Dual antiplatelet therapy with aspirin plus<br />
a P2Y 12 inhibitor, whatever it is, has been shown<br />
to be very efficacious to reduce the rate <strong>of</strong><br />
events.<br />
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<strong>Triple</strong> antiplatelet therapy has an<br />
added value, but unfortunately, it is underused<br />
particularly in the setting <strong>of</strong> acute coronary<br />
syndromes.<br />
This underuse <strong>of</strong> antiplatelet therapy is<br />
probably detrimental for such patients. The<br />
right subset <strong>of</strong> patients for such therapies must<br />
be defined.<br />
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Choosing the Appropriate Patient<br />
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<strong>Safety</strong> <strong>of</strong> <strong>Triple</strong> <strong>Antiplatelet</strong> <strong>Therapy</strong><br />
As we start getting more and more<br />
powerful antiplatelet drugs, the risk <strong>of</strong><br />
bleeding complications increase.<br />
So the clinical focus has shifted a<br />
little bit, not just to focus on thrombotic<br />
risk, but also on bleeding risk.<br />
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PCI US Registry<br />
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<strong>Safety</strong> <strong>of</strong> <strong>Triple</strong> <strong>Antiplatelet</strong> <strong>Therapy</strong><br />
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EARLY ACS was designed to<br />
examine the efficacy <strong>of</strong> routine eptifibatide<br />
versus delayed provisional use during PCI<br />
in patients with high-risk ACS.<br />
The overall data showing that as a<br />
strategy, early use <strong>of</strong> eptifibatide did not<br />
result in a significant reduction in 96-hour<br />
death, MI, or recurrent ischemia, with an<br />
overall increase risk <strong>of</strong> bleeding.<br />
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<strong>Safety</strong> <strong>of</strong> <strong>Triple</strong> <strong>Antiplatelet</strong> <strong>Therapy</strong><br />
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Whether or not the patient receives<br />
clopidogrel did not seem to impact the<br />
bleeding risk. It was really driven by the<br />
GPIIb/IIIa.<br />
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<strong>Safety</strong> <strong>of</strong> <strong>Triple</strong> <strong>Antiplatelet</strong> <strong>Therapy</strong><br />
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If the patient receives GP IIb/IIIa early,<br />
they’re going to bleed whether or not they<br />
receive upstream clopidogrel, and that's<br />
regardless <strong>of</strong> which definition you use.<br />
TIMI-Major bleeding, GUSTO moderate-tosevere,<br />
or if you look at a marker for<br />
bleeding complications, which is blood<br />
transfusion.<br />
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From the GRACE Registry, the risk<br />
<strong>of</strong> 30-day mortality, is higher among<br />
patients who bleed, as is the risk <strong>of</strong> 30-day<br />
reinfarction.<br />
Now this is true actually even for<br />
patients who don't undergo procedures, but<br />
the majority <strong>of</strong> the bleeding risk is driven by<br />
the procedure that takes place in ACS<br />
patients.<br />
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<strong>Safety</strong> <strong>of</strong> <strong>Triple</strong> <strong>Antiplatelet</strong> <strong>Therapy</strong><br />
R&M Solutions<br />
GRACE Registry<br />
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<strong>Safety</strong> <strong>of</strong> <strong>Triple</strong> <strong>Antiplatelet</strong> <strong>Therapy</strong><br />
R&M Solutions<br />
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<strong>Safety</strong> <strong>of</strong> <strong>Triple</strong> <strong>Antiplatelet</strong> <strong>Therapy</strong><br />
R&M Solutions<br />
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<strong>Safety</strong> <strong>of</strong> <strong>Triple</strong> <strong>Antiplatelet</strong> <strong>Therapy</strong><br />
R&M Solutions<br />
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But there are patients who are<br />
candidates for powerful antithrombotic<br />
therapies; patients with ST-elevation,<br />
patients who have high clinical risk<br />
factors.<br />
What are strategies that we can<br />
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implement?<br />
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Gender<br />
Age<br />
S. Cr mg/dl<br />
TLC<br />
Anemia<br />
Presentation<br />
Antith med<br />
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The biggest drivers <strong>of</strong> bleeding risks<br />
in this risk score, as in almost every other<br />
risk score, is age and sex. Also renal<br />
dysfunction has a very, very highly<br />
predictive value in some risk modules.<br />
For age, the data from the CRUSADE<br />
may be 5 years old, but it's remarkable<br />
how <strong>of</strong>ten antithrombotic drugs are actually<br />
overdoses in patients who are older.<br />
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For sex, women specifically have<br />
been studied, because it’s a consistent risk<br />
factor for bleeding complications; it does<br />
appear that female patients who get<br />
excess dosing are more likely to bleed.<br />
In fact, 25% <strong>of</strong> the increased risk <strong>of</strong><br />
bleeding in female patients with ACS can<br />
be explained by overdosing.<br />
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Pay attention also to the duration <strong>of</strong><br />
the treatment. The longer you treat the<br />
patient who is on anticoagulants, the longer<br />
you treat the patient with GPIIb/IIIa<br />
inhibitors, the higher the risk <strong>of</strong> bleeding.<br />
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Another thing is vascular<br />
complications, because these are<br />
intimately tied-in with bleeding<br />
complications in patients with acute<br />
coronary syndromes.<br />
The US data looking at patients who<br />
are over the age <strong>of</strong> 65 who are eligible for<br />
Medicare, the vascular complications are<br />
the most common complications in patients<br />
undergoing PCI.<br />
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There is a suggestion that there is a<br />
reduced risk <strong>of</strong> mortality. That is almost<br />
entirely driven by a reduction in blood<br />
transfusion.<br />
As transfusion is associated with<br />
increased morality, so a strategy that<br />
reduces transfusion, it is reasonable to<br />
think that it may reduce mortality.<br />
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