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Pharmacology in Acute Coronary Syndromes: Anti-platelet Agents

Pharmacology in Acute Coronary Syndromes: Anti-platelet Agents. Tim Kinnaird, University Hospital Wales, Cardiff and Vale NHS Trust. NO CONFLICT OF INTEREST TO DECLARE. Intra-Coronary Thrombus. What are the Characteristics of an Ideal Anti-Platelet Agent?. Effective. Rapid Onset.

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Pharmacology in Acute Coronary Syndromes: Anti-platelet Agents

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  1. Pharmacology in Acute Coronary Syndromes: Anti-platelet Agents Tim Kinnaird, University Hospital Wales, Cardiff and Vale NHS Trust

  2. NO CONFLICT OF INTEREST TO DECLARE

  3. Intra-Coronary Thrombus

  4. What are the Characteristics of an Ideal Anti-Platelet Agent? Effective Rapid Onset Rapid Offset Safe Cheap Works in all patients

  5. Effectiveness of Clopidogrel PCI-Cure, Credo, PCI-Clarity meta-analysis (7000 patients vast majority presented with ACS) JAMA 2005;294:1224-1232

  6. Effectiveness of Clopidogrel Circulation. 2005;112:2946-2950

  7. Effectiveness of Clopidogrel 255 patients (25% ACS) preloaded 300 vs. 600mg 4-8hrs pre PCI Circulation 2005;111:2099-106

  8. Effectiveness of Clopidogrel 292 ACS pts 300 vs. 600mg clopidogrel at least 12-hours pre PCI JACC 2006;48:1339-45

  9. What are the Characteristics of an Ideal Anti-Platelet Agent? Effective Rapid Onset Rapid Offset Safe Cheap Works in all patients

  10. Onset of Action of Clopidogrel 300mg load and pre-treatment Median 10 days PCI-Cure Mean 9.8hrs CREDO p=NS

  11. Onset of Action of Clopidogrel Early and Sustained Dual Oral Antiplatelet Therapy Following Percutaneous Coronary Intervention: Clopidogrel for Reduction in Events During Observation (CREDO) trial JAMA 2002;288:2411-20 JACC 2006;47:939-43

  12. Onset of Action of Clopidogrel ALBION study In-vitro analysis JACC 2006;48:931-8

  13. Onset of Action of Clopidogrel 2159 low and moderate risk patients, ACS excluded Preload with 600mg at least 2-hours before PCI NEJM 2004;350:232-8 JACC 2004;44:2133-36

  14. Onset of Action of Clopidogrel 2022 pts with NSTEACS 600mg clopidogrel at least 2-hours pre PCI JAMA 2006;295:1531-38

  15. Armyda 5 600mg clopidogrel 6-hours pre-PCI vs. 600mg clopidogrel after diagnostic angiogram Prelim data presented suggested no difference between 2 groups Full peer review data at ACC late-breaking trials

  16. CREDO ACC/AHA/SCAI 2005 guidance states: ESC 2005 guidance states: Different question Different question ISAR-REACT Circulation 2006;113;156-175 ISAR-REACT CURE PCI-CURE What do the Guidelines Say About Clopidogrel Pretreatment in PCI for ACS?

  17. CONCLUSIONS WHAT WE KNOW WE KNOW - 300mg loading dose should be given at least 15-hours before PCI in ACS patients - 600mg dose is probably more effective than 300mg dose - troponin +ve ACS pts should receive abciximab in addition to 600mg of clopidogrel regardless of timing

  18. CONCLUSIONS WHAT WE KNOW WE DON’T KNOW - what is the optimal timing of 600mg dose of clopidogrel in ACS patients undergoing PCI - whether early enough loading with 600mg clopidogrel would obviate the need for further adjunctive antiplatelet agents - whether higher still doses of clopidogrel are better

  19. FINALLY Newer oral antiplatelet agents include: Prasugrel (thienopyridine) Cangrelor (ADP analogue) AZD6140 (direct inhibitor of P2Y12 receptor) SCH530384 (PAR blocker)

  20. JUMBO-TIMI 26 904 patients in safety study 300 Circulation 2005;111:3366-73 Prasugrel as an Alternative to Clopidogrel More rapid onset to greater levels of IPA Less non-responders

  21. Prasugrel as an Alternative to Clopidogrel TRITON TIMI-38 13,000 ACS patients undergoing PCI Randomised to prasugrel 60/10 or clopidogrel 300/75 Loading dose given between randomisation and completion of PCI Primary endpoint time to first CV death, MI or CVA Results expected 2008

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