ΠΤΡΟ Ν. ΠΑΠΑΪΩΑΝΝΟΤ MD. PHD. FESC · safety end point (Thrombolysis in Myocardial...
Transcript of ΠΤΡΟ Ν. ΠΑΠΑΪΩΑΝΝΟΤ MD. PHD. FESC · safety end point (Thrombolysis in Myocardial...
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NOVEL ANTIPLATELET
DRUGS
IN ACS
ΠΤΡΟ Ν. ΠΑΠΑΪΩΑΝΝΟΤ MD. PHD. FESC
ΕΙΔΙΚΟ ΚΑΡΔΙΟΛΟΓΟ
ΔΙΔΑΚΣΩΡ ΑΠΘ
ΑΝΑΠΛΗΡΩΣΗ ΔΙΕΤΘΤΝΣΗ ΚΑΡΔΙΟΛΟΓΙΚΗ
ΚΛΙΝΙΚΗ ΝΑΤΣΙΚΟΤ ΝΟΟΚΟΜΕΙΟΤ ΑΘΗΝΩΝ
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ΠΕΡΙΕΧΟΜΕΝΑ
1. Novel antiplatelet agents-Mechanism of action
2. Ticagrelor
3. Prasugrel
4. Cangrelor
5. Elinogrel
6. Guidelines (ESC-AHA)
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ΠΕΡΙΕΧΟΜΕΝΑ
1. Novel antiplatelet agents-Mechanism of action
2. Ticagrelor
3. Prasugrel
4. Cangrelor
5. Elinogrel
6. Guidelines (ESC-AHA)
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August 30, 2009 at 08.00 CET
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PLATO background
In NSTE-ACS and STEMI, current guidelines
recommend 12 months aspirin and clopidogrel
Efficacy of clopidogrel is hampered by
slow and variable transformation to the active metabolite
modest and variable platelet inhibition
increased risk of bleeding
risk of stent thrombosis and MI in poor responders
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K-M estimate of time to first primary efficacy
event (composite of CV death, MI or stroke)
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Secondary efficacy endpoints
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Stent thrombosis
Ticagrelor
(n=5,640)
Clopidogrel
(n=5,649)
HR
(95% CI) p value
Stent thrombosis, n (%)
Definite
Probable or definite
Possible, probable, definite
71 (1.3)
118 (2.1)
155 (2.8)
106 (1.9)
158 (2.8)
202 (3.6)
0.67 (0.50–0.91)
0.75 (0.59–0.95)
0.77 (0.62–0.95)
0.009
0.02
0.01
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Time to major bleeding – primary
safety event
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Total major bleeding
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Conclusions Reversible, more intense P2Y12 receptor inhibition for one year
with ticagrelor in comparison with clopidogrel in a broad
population with ST- and non-ST-elevation ACS provides
Reduction in myocardial infarction and stent thrombosis
Reduction in cardiovascular and total mortality
No change in the overall risk of major bleeding
Ticagrelor is a more effective alternative than clopidogrel
for the continuous prevention of ischaemic events, stent
thrombosis and death in the acute and long-term treatment
of patients with ACS
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ΠΕΡΙΕΧΟΜΕΝΑ
1. Novel antiplatelet agents-Mechanism of action
2. Ticagrelor
3. Prasugrel
4. Cangrelor
5. Elinogrel
6. Guidelines (ESC-AHA)
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TRITON TIMI-38
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Study Overview
Antiplatelet therapy with aspirin and a thienopyridine is a key component in the management of acute coronary syndromes
This trial compared a novel, potent thienopyridine (prasugrel) with the standard thienopyridine (clopidogrel) in patients with acute coronary syndromes scheduled to have a coronary intervention
Prasugrel led to better cardiovascular outcomes, but at the expense of more bleeding, including fatal bleeding
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A shows data for the primary efficacy end point (death from cardiovascular
causes, nonfatal myocardial infarction [MI], or nonfatal stroke) and for the key
safety end point (Thrombolysis in Myocardial Infarction [TIMI] major bleeding not
related to coronary-artery bypass grafting) (bottom) during the full follow-up
period. The hazard ratio for prasugrel, as compared with clopidogrel, for the primary
efficacy end point at 30 days was 0.77 (95% confidence interval [CI], 0.67 to 0.88;
P<0.001) and at 90 days was 0.80 (95% CI, 0.71 to 0.90; P<0.001).
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TRITON TIMI 38
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TRITON Diabetic Subgroup
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TRITON STEMI cohort
Primary EP (CV death, MI and stroke at 15 months)
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TRITON Net Clinical Benefit
Bleeding Risk Subgroups
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Conclusion
In patients with acute coronary syndromes with scheduled percutaneous coronary intervention, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding
Overall mortality did not differ significantly between treatment groups
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ΠΕΡΙΕΧΟΜΕΝΑ
1. Novel antiplatelet agents-Mechanism of action
2. Ticagrelor
3. Prasugrel
4. Cangrelor
5. Elinogrel
6. Guidelines (ESC-AHA)
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CANGRELOR
A NOVEL INTRAVENOUS ANTIPLATELET AGENT??
•ATP analogue
•Relatively resistant to the
breakdown of endonucleotidases
•Not require metabolic activation
• Reversible competitive
antagonist
•Administered intravenously
•Th<5 min
•Rapid onset of effect
•Major use in the acute setting
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CANGRELOR
CHAMPION PCI – CHAMPION PLATFORM
Negative Trials But Some Positive Angles for Cangrelor?
Both trials were discontinued prematurely due to insufficient evidence of the
clinical effectiveness of cangrelor.
There were, however, reductions in stent thrombosis and death from any
cause.
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CHAMPION PHOENIX
Cangrelor
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CHAMPION PHOENIXCangrelor Cuts Complications at PCI vs Clopidogrel in
CHAMPION-PHOENIX; Bleeding a Caution
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CANGRELOR
February 12, 2014
Administration (FDA) advisory panel voted 7 to 2 that cangrelor (the Medicines Company, Parsippany, NJ), an intravenously administered antiplatelet agent, should not be approved for the reduction of thrombotic cardiovascular events in patients with coronary artery disease undergoing PCI.
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ΠΕΡΙΕΧΟΜΕΝΑ
1. Novel antiplatelet agents-Mechanism of action
2. Ticagrelor
3. Prasugrel
4. Cangrelor
5. Elinogrel
6. Guidelines (ESC-AHA)
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ELINOGREL The only reversible and competitive P2Y12 receptor antagonist
Direct-acting: no metabolic activation required
Available for intravenous and oral administration, enabling acute and chronic use
Immediate and near maximal platelet inhibition achieved with IV
Duration of action
Half-life: 12 hours
No major CYP metabolism – low potential for drug-drug interactions (including PPIs)
Balanced clearance: 50% renal; 50% hepatic (10% metabolized to pharmacologically inactive metabolite)
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INNOVATE PCI-treatment schema
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Clinical Endpoints
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Bleeding at 24 hours
*mainly on access site
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Adverse Events
* Dyspnea was generally mild, transient, and infrequently led to discontinuation
^ Most cases occurred within first 60 days and were asymptomatic; All cases resolved, even
when treatment was continued; No Hy’s Law cases.
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Conclusions
IV and oral elinogrel result in greater and more rapid antiplatelet effect than clopidogrel during both the acute and chronic phase of therapy
No excess TIMI major or minor bleeding at both the 24-hr and 120-day timepoints
Dose-dependent trend of increase in less severe bleeds (Bleeding Requiring Medical Attention), mostly occurring at the vascular access site in the peri-procedural period
No significant differences in efficacy at 24 hrs or 120 days (trial not powered for efficacy)
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ΠΕΡΙΕΧΟΜΕΝΑ
1. Novel antiplatelet agents-Mechanism of action
2. Ticagrelor
3. Prasugrel
4. Cangrelor
5. Elinogrel
6. Guidelines (ESC-AHA)
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Conclusions
NEW ANTIPLATELET AGENTS ARE:
Effective
Rapid
Safe
And,,,In the future they could lead to decrease of the duration of DAPT in
patients with with ACS and PCI with stent implantation if combined
with new generation stents
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