If I had an acute coronary syndrome, which antiplatelet agent would I prefer?

1. If I had an acute coronary syndrome, which antiplatelet agent would I prefer? Giuseppe Biondi Zoccai, MD, FSICI-GISE Division of Cardiology University of Modena and Reggio Emilia gbiondizoccai@gmail.com

2. LEARNING GOALS • SCOPE OF THE PROBLEM • MENU A LA CARTE OR TABLE D’HOTE? • MY OWN RECIPE

3. LEARNING GOALS • SCOPE OF THE PROBLEM • MENU A LA CARTE OR TABLE D’HOTE? • MY OWN RECIPE

4. ACUTE CORONARY SYNDROMES Plaque rupture Old terms Stable angina Unstable angina Q-MI Non-Q MI New terms STEMI Atherothrombosis UA/NSTEMI Days Weeks Minutes Hours Antithrombotic therapy & (selectively) invasive management Reperfusion (thrombolysis and/or PTCA)

5. SCOPE OF THE PROBLEM Bleeding Peri-procedural complications Thrombotic events Myocardial ischemia

6. SCOPE OF THE PROBLEM Bleeding Peri-procedural complications Thrombotic events Myocardial ischemia

7. SCOPE OF THE PROBLEM

8. SCOPE OF THE PROBLEM: AMI Capewell et al, Heart 2006 Capewell et al, Heart 2006

9. SCOPE OF THE PROBLEM: UNSTABLE ANGINA Capewell et al, Heart 2006 Capewell et al, Heart 2006

10. PATHWAYS TO THROMBOSIS * * * * Myers, BUMC Proceedings 2005 Myers, BUMC Proceedings 2005

11. MULTIPLE VULNERABLE CORONARY PLAQUES IN PATIENTS WITH AMI Asakura et al, J Am Coll Cardiol 2001 Asakura et al, J Am Coll Cardiol 2001

12. MULTIPLE RUPTURED CORONARY PLAQUES IN PATIENTS WITH ACS

13. ENDOTHELIALIZATION OF STENT STRUTS SES BMS Guagliumi et al, Ital Heart J 2003 Guagliumi et al, Ital Heart J 2003

14. ON TOP OF THIS:VARIABILITY IN RESPONSE TO ANTITHROMBOTIC THERAPY

15. VARIABILITY IN RESPONSE Change in ADP-Induced Platelet Aggregation 75 mg chronic dosing Maximal aggregation 5 µmol/L ADP (%) following 600 mg loading dose 100 N=1001 N=544 80 60 Number of Patients 40 20 0 0 2 4 6 8 10 Time from loading dose to cath (h) Relative change in aggregation Serebruany et al, J Am Coll Cardiol 2005 Hochholzer et al, Circulation 2005

16. GENETIC VARIABILITY IN RISK OF STENT THROMBOSIS Mega et al, New Engl J Med 2009

17. FAILING STENTS: THROMBOSIS VS RESTENOSIS Schuchman, New Engl J Med 2006

18. MECHANISMS OF THROMBOSIS: VIRCHOW'S TRIAD BLOOD FLOW VESSEL

19. MECHANISMS OF STENT THROMBOSIS PATIENT FACTORS LESION FACTORS PROCEDURAL & MEDICAL RX FACTORS

20. PREDICTING THROMBOSIS ACCORDING TO DIABETES Machecourt et al, J Am Coll Cardiol 2009

21. PREDICTING THROMBOSIS ACCORDING TO STENT LENGTH Moreno et al, J Am Coll Cardiol 2005

22. PREDICTORS OF STENT THROMBOSIS AFTER ACS OR Van Werkum et al, J Am Coll Cardiol 2009

23. LEARNING GOALS • SCOPE OF THE PROBLEM • MENU A LA CARTE OR TABLE D’HOTE? • MY OWN RECIPE

24. ASPIRIN

25. ASPIRIN IN UNSTABLE ANGINA 0.25 Placebo 0.20 Risk ratio after 1 year 0.5295% Cl 0.37–0.72 (P=0.0001) 0.15 Probability of death or MI 0.10 ASA 75 mg 0.05 0.00 0 3 6 9 12 Months Wallentin et al, JACC 1991

26. CLOPIDOGREL

27. PCI-CURE 12.6% 1.9% ARR 31% RRR P=0.002 N=2,658 0.15 Placebo Clopidogrel 8.8% 0.10 Cumulative hazard rates for CV death/MI 0.05 0.0 0 100 200 300 400 10 40 Days of follow-up a b a = median time PCI (10 days) b = 30 days after median time of PCI Mehta et al, Lancet 2001

28. IMPACT OF ANTIPLATELET THERAPY INTENSITY 30-day results of the CURRENT-OASIS 7 Trial Mehta et al, Lancet 2010

29. SUMMARY OF EVIDENCE ON CLOPIDOGREL LOADING Lotrionte et al, Am J Cardio 2007;100:1199-1206

30. ABCIXIMAB

31. BENEFITS OF ABCIXIMAB IN ACS PATIENTS PRETREATED WITH 600 MG CLOPIDOGREL 600 mg clopidogrel 500 mg ASA >2 h before PCI * *Death/MI/urgent TVR Kastrati et al, JAMA 2006

32. PRASUGREL

33. THE TRITON-TIMI 38 2.31% 2 CLOPIDOGREL 1.5 % of subjects having DES thrombosis Hazard ratio 0.36 [0.22-0.58] P<0.0001 0.84% 1 PRASUGREL 0.5 0 Days 0 50 100 150 200 250 300 350 400 450

34. THE TRITON-TIMI 38 Wiviott et al, Lancet 2008;371:1353-63

35. TICAGRELOR

36. THE PLATO TRIAL Wallentin et al, NEJM 2009

37. THE PLATO TRIAL Wallentin et al, NEJM 2009

38. THE PLATO TRIAL Wallentin et al, NEJM 2009

39. WHEN IS MUCH TOO MUCH?

40. LEARNING GOALS • SCOPE OF THE PROBLEM • MENU A LA CARTE OR TABLE D’HOTE? • MY OWN RECIPE

41. INDIRECT COMPARISON OF PRASUGREL VS. TICAGRELOR Funnel plots comparing prasugrel vs. ticagrelor for the risk of key clinical events. Odds ratios (OR) <1.0 favor prasugrel, whereas odds ratios>1.0 favor ticagrelor.

42. Intra-hospital transfer ER Out-of-hospital EMS Appraisal of thrombotic and bleeding risks – aspirin unless bleeding risk prohibitive  thrombotic risk  bleeding risk  thrombotic risk  bleeding risk  thrombotic risk  bleeding risk  thrombotic risk  bleeding risk Clopidogrel or Ticagrelor Prasugrel or Ticagrelor Wait-and-see Wait-and-see Coronary angiography CABG Medical Rx pPCI with BMS pPCI with DES Clopidogrel, Prasugrel or Ticagrelor Clopidogrel, Prasugrel or Ticagrelor Clopidogrel or Ticagrelor Ticagrelor

43. TAKE HOME MESSAGE THROMBOSIS BLEEDING

44. ThankyouforyourattentionForanycorrespondence: gbiondizoccai@gmail.comForthese and furtherslides on thesetopicsfeel free tovisit the metcardio.org website:http://www.metcardio.org/slides.html