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Dia 2
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Mortality in hospital and at 6 months in low, intermediate and high risk categories in registry populations according to the GRACE Risk score http://www.outcomes.org/grace
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Question: Strategy ?
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Relative risk of all cause of mortality
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Management Strategy
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Time to catheterization (hrs)
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Dia 8
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A.S.A.P < 24 h vs delayed > 36h - ACS met 2/3 > 60 y, pos marker (76%), ischemic ECG (80%) and revasc possible
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No early hazard!
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GRACE > 141 14% 21% p=0.009
Major bleeds 3.1 3.5% p=0.53
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Early (≤24 h, median=14h) or delayed intervention ( ≥36 h, median=50h)
N=3000
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Early (≤24 h, median=14h) or delayed intervention ( ≥36 h, median=50h)
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Why not immediately
“STEMI-like”?
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ABOARD study design
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Index ACS event
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In-hospital medications
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Time to catheterization (hrs)
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Primary EP (peak of troponin I)
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Composite Ischemic Endpoints at 1 month
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Safety outcomes at 1 month
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Hospital stay
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Summary: TIMACS and ABOARD
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Question: Strategy ?
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Q: GPIIbIIIa inhibitors ? When ?
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GPIIbIIIa Inhibitors
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Efficacity GPIIBIIIA in NSTE ACS only if PCI !!!
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N=2022
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If GPIIbIIIa:
- Upstream for all high risk NSTE ACS ?
- or selectively downstream if PCI ?
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N=9492
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Delayed Provisional GPIIbIIIa:
Same Ischemic benefit
Lower bleeding risk
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30-day Death or MI Prespecified Subgroups
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Summary for GPIIbIIIa
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Q: GPIIbIIIa inhibitors ? When ?
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Q: Antiplatelet Therapy: P2Y12 inhibitors in CCU ?
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Alternatives Molecules
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Montalescot et al. JACC 2006
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Q: Antiplatelet Therapy: P2Y12 inhibitors in CCU ?
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Antiplatelet Drugs
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Study Design, Flow and Compliance
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Clopidogrel: Double vs Standard Dose Primary Outcome and Components
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Clopidogrel: Double vs Standard Dose
Primary Outcome: PCI Patients
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Clopidogrel Double vs Standard Dose Bleeding PCI Population at 30 days
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Conclusions Clopidogrel Dose Comparison
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ACS (STEMI or UA/NSTEMI) & Planned PCI
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Primary Endpoint: CV Death,MI,Stroke
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Balance of Efficacy and Safety
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ISCHEMIC BENEFIT: subgroups
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Diabetic Subgroup
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Ischemic Risk
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BLEEDING RISK: subgroups
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Tailored for Bleeding Risk ?
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P2Y12 inhibitors for PCI/ACS in 2011
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Q: Antiplatelet Therapy: P2Y12 inhibitors in CCU ?
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Platelet Function Tests
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Composite of death, non-fatal myocardial infarction, definite stent thrombosis and stroke
POPular study JAMA 2010
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Cut-Off values Based on Clinical Endpoints
in Prospective Studies
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Risk for recurrent events concentrated in patients with highest on-treatment reactivity
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POPular Risc Score
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Ticagrelor compared with clopidogrel in patients with acute coronary syndromes – the PLATO trial
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Ticagrelor (AZD 6140): an oral reversible P2Y12 antagonist
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PLATO study design
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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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Time to major bleeding – primary safety event
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Non-CABG and CABG-related major bleeding
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Safety = TIMI Major Non-CABG Bleeds (12-15 months)
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Conclusions
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2011 CURRENT vs PLATO vs TRITON
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Platelet Aggregation at 4 hours
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TRITON and PLATO
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Safety = TIMI Major Non-CABG Bleeds (12-15 months)
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Tailor-made medicine?
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Marked interindividual response to antiplatelet drugs
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Residual or On-Treatment Platelet Reactivity
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Do Platelet Function Assays Predict Clinical Outcomes in clopidogrel pretreated patients undergoing elective PCI
The POPular-study. JAMA 2010;303:754-62
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Tests more physiological shear-dependent
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POPular Risk Score
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Rate of CABG patients and TIMI Major Bleeds
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Summmary: P2Y12 inhibition for tomorrow
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Compliance and ST
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With more potent P2Y12 inhibitors: How to reduce Bleeding Risk in ACS ?
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Low Dose of Aspirin
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ASA Dose Comparison Primary Outcome and Bleeding
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Use of PPI
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Radial Access
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Case
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3/3/2011
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3/3/2011
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Similar for DES
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MACC with BMS and non-cardiac surgery N=899
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Bleeds with DES and Non-cardiac Surgery
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Bridging?
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Summary for ACS: 2011
|
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Discharge therapy
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Tailored Therapy PCI in ACS ?
|
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Discontinue antithrombotica
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