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 Safe Cheap Works in all patients Rapid Offset

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

Effectiveness of Clopidogrel Circulation. 2005;112:

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

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

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

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

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: JACC 2006;47:939-43

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

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:

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

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

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

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 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 CONCLUSIONS

FINALLY Newer oral antiplatelet agents include: Prasugrel (thienopyridine) Cangrelor (ADP analogue) AZD6140 (direct inhibitor of P2Y 12 receptor) SCH (PAR blocker)

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

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