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Trial Vignettes

Trial Vignettes . TRITON-TIMI 38 ARMYDA 4 + 5 OPTIMA. Cameron G Densem. NO CONFLICT OF INTEREST TO DECLARE. TR ial to Assess I mprovement in T herapeutic O utcomes by Optimizing Platelet Inhibitio N with Prasugrel- TIMI 38. Dual antiplatelet therapy Limitations of Clopidogrel

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Trial Vignettes

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  1. Trial Vignettes TRITON-TIMI 38 ARMYDA 4 + 5 OPTIMA Cameron G Densem

  2. NO CONFLICT OF INTEREST TO DECLARE

  3. TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-TIMI38 • Dual antiplatelet therapy • Limitations of Clopidogrel • Prasugrel, novel ADP inhibitor • More rapid, consistent and effective • JUMBO-TIMI 26 Bleeding MACE

  4. 13 608 ACS Patients Scheduled PCI Known anatomy Clopidogrel 300mg Aspirin 75-162mg Prasugrel 60mg Loading Exclusions: Increased bleed risk Anaemia Low platelets Intracranial pathology Thienopyridine 5/7 PCI Aspirin 75-162mg Prasugrel 10mg Chronic 6-15 months Clopidogrel 75mg Primary endpoint: CV Death Non-fatal MI Non-fatal CVA Secondary endpoints: Stent thrombosis (ARC) Bleeding Primary endpoint and TVR

  5. 99% had PCI 94% had at least 1 stent 47% at least 1 DES Median FU 14.5 mths 2.2% absolute reduction 19% relative reduction

  6. Prasugrel Clopidogrel HR P Cardiovascular Death 2.1% 2.4% 0.89 0.31 Non fatal MI 7.3% 9.5% 0.76 <0.001 10 Endpoint diabetics 12.2% 17.0% 0.70 <0.001 10 Endpoint non- diabetics 9.2% 10.6% 0.86 0.02 Urgent TVR 2.5% 3.7%% 0.66 <0.001 Stent thrombosis 1.1% 2.4% 0.48 <0.001 (def/prob ARC) BMS 0.52 <0.001 DES 0.43 <0.001

  7. Bleeding Prasugrel Clopidogrel HR P Non CABG TIMI Major 2.4% 1.8% 1.32 0.03 Life threatening 1.4% 0.9% 1.52 0.01 Fatal 0.4% 0.1% 4.19 0.002 Intracranial 0.3% 0.3% 1.12 0.74 Major/minor TIMI 5.0% 3.8% 1.31 0.002 Transfusion 4.0% 3.0% 1.34 <0.001 CABG TIMI major 13.4% 3.2% 4.73 <0.001

  8. Post Hoc Analysis Prasugrel Clopidogrel HR P Prev CVA/TIA 23.0% 16.0% 1.54 0.04 Age >75 % % 0.99 0.92 Weight <60Kg % % 1.03 0.89 Age<75, Weight >60Kg 10.2%12.5% 0.80 <0.001 No CVA/TIA End point: death any cause, non-fatal MI/CVA, non-CABG related nonfatal TIMI major bleed

  9. Conclusions • Reduction in ischaemic events • At a cost of increased bleeding • Subgroups • Diabetics • Age, CVA, body weight • For every 100 patients treated: • 23 MIs prevented • Excess of 6 non CABG TIMI major bleeds “…clinicians need to weigh the benefits and risks of intensive inhibition of platelet aggregation….”

  10. Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty 4 and 5 • Debate surrounding optimal dosage and timing of antiplatelet agents around time of PCI • Potential benefit of 600mg Clopiogrel loading Death MI TVR ARMYDA-2

  11. 350 patients Clopidogrel naive Angina or NSTEMI Unknown anatomy ARMYDA-5 Clopidogrel 600mg Pretreatment n=174 Coronary Angiography PCI indicated 4-8hrs Pre- PCI Coronary Angiography Clopidogrel 600mg treatment n=176 Coronary Angioplasty 30 day Primary endpoint: CV Death Non-fatal MI TVR Secondary endpoints: Bleeding Biomarker release

  12. 11% 8% Composite primary endpoint: 30 day death, MI, TVR (all events MIs) p=0.56 5% Minor bleeding at 30 days 4% p=ns

  13. 464 patients on Clopidogrel>10 days Angina or NSTEMI Unknown anatomy ARMYDA-4 Clopidogrel Reloading 600mg n=230 4-8hrs Pre- PCI Placebo n=234 Exclusions: Primary PCI High bleed risk Low platelets Recent CABG Coronary Angiography CABG n=42 PCI n=180 PCI n=180 Medical n=62 30 day Primary endpoint: CV Death Non-fatal MI TVR Secondary endpoints: Biomarker release Bleeding

  14. Composite primary endpoint: 30 day death, MI, TVR Individual events at 30 days 8% % 8% % 7% 7% p=0.96 MI definition: post-procedural increase of CK-MB >3 times above UNL Post PCI peak levels of Troponin I (ng/ml) Bleeding 4% 4% % Placebo 0.52 +/- 2.2 0.39 +/- 1.1 Clopidogrel

  15. Conclusions • 600mg Clopidogrel preloading confers no benefit relative to intra loading • 600mg Clopidogrel reloading confers no extra benefit if on chronic therapy • Small sample sizes

  16. OPtimal TIMing of PCI in Unstable Angina • Current guidelines recommend an early invasive strategy in high risk NSTE-ACS • The precise timing of early PCI is controversial. • Immediate PCI may prevent (spontaneous) cardiac events • Deferred PCI may lead to less peri-procedural complications

  17. High Risk ACS Coronary Angiography N=251 OPTIMA Exclusions n=109: No significant CAD 55 CABG 27 ISR 9 Clinically driven immediate PCI 8 Culprit lesion not amenable for PCI 6 CTO 4 Abciximab Aspirin Clopidogrel Immediate PCI n=73 Deferred PCI n=69 30 day Primary endpoint: CV Death Non-fatal MI TVR

  18. Deferment

  19. Primary Endpoint 30 days: CV Death, Non-fatal MI, TVR No Mortality

  20. Infarct Size peak CKMB: p<0.01 % CKMB (median): 9.8 (ng/L) 4.9 (ng/L)

  21. Conclusions • Immediate PCI increases rate of “peri-procedural” CK-MB release • Small, select group of patients • Preliminary data • Underpowered, planned to recruit 600 • ?CK-MB best biomarker • How long waiting for first cath

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