1. Antiplatelet therapy and PCI in unstable angina and NSTEMI Giuseppe Biondi Zoccai Divisione di Cardiologia, Università di Torino gbiondizoccai@gmail.com

2. Disclosure No funding or conflict of interest to declare

3. Topics Introduction and pathophysiologic insights Antiplatelet regimens Triage to invasive management State of the art PTCA

4. Topics Introduction and pathophysiologic insights Antiplatelet regimens Triage to invasive management State of the art PTCA

5. Antithrombotic therapy & (selectively) invasive management Stable angina Unstable angina Reperfusion (thrombolysis and/or PTCA) Minutes Hours Days Weeks STEMI UA/NSTEMI Atherothrombosis New terms Old terms Plaque Plaquerupture Non-Q MI Q-MI Acute coronary syndromes

6. Scope of the problem Thrombotic events Myocardial ischemia Bleeding Peri-procedural complications

7. Scope of the problem Thrombotic events Myocardial ischemia Bleeding Peri-procedural complications

8. Scope of the problem

9. Scope of the problem: AMI Capewell et al, Heart 2006

10. Scope of the problem: unstable angina Capewell et al, Heart 2006

11. Pathways to thrombosis * * * * Myers, BUMC Proceedings 2005

12. Multiple vulnerable coronary plaques in patients with AMI Asakura et al, J Am Coll Cardiol 2001

13. Multiple ruptured coronary plaques in patients with ACS

14. Endothelialization of stent struts Guagliumi et al, Ital Heart J 2003 SESBMS

15. Topics Introduction and pathophysiologic insights Antiplatelet regimens Triage to invasive management State of the art PTCA

16. 0.00 0.05 0.10 0.15 0.20 0.25 036912 Months Probability of death or MI Placebo ASA 75 mg Risk ratio after 1 year 0.52 95% Cl 0.37–0.72 (P=0.0001) Wallentin et al, JACC 1991 Aspirin in unstable angina

17. Theroux et al, NEJM 1988 UF Heparin in NSTEACS

18. LMW heparin in NSTEACS

19. Cumulative hazard rates for CV death/MI Days of follow-up a = median time PCI (10 days) b = 30 days after median time of PCI 0.15 0.10 0.05 0.0 010010 0 40 100200300400 ab PlaceboClopidogrel 12.6% 8.8% 1.9% ARR 31% RRR P=0.002 N=2,658 Mehta et al, Lancet 2001 PCI-CURE Substudy

20. Cuisset et al, JACC 2006 *P=0.02 N=146 1-Month Clopidogrel loading in pts with ACS undergoing PCI

21. Kastrati et al, JAMA 2006 Benefits of abciximab in ACS patients pretreated with 600 mg clopidogrel *Death/MI/urgent TVR * 600 mg clopidogrel 500 mg ASA >2 h before PCI

22. 13,800 pts Endpoint: Death/MI/urgentTVR Bivalirudin in ACS: the ACUITY Trial Stone et al, TCT 2006

23. ESC guidelines

24. 2002 ESC guidelines on NSTEACS Bertrand et al, EHJ 2002

25. 2002 ESC guidelines on NSTEACS

26. Silber et al, EHJ 2005 2005 ESC guidelines on PCI

27. Overwhelming complexity?

28. Bertrand et al, EHJ 2002; Silber et al, EHJ 2005 ESC guidelines: a synthesis ASPIRIN:ASPIRIN: 500 mg oral or 300 mg IV loading dose, followed by 75-100 mg daily lifelong CLOPIDOGREL:CLOPIDOGREL: 300 to 600 mg loading dose ASAP, followed by 75 mg daily for 9-12 months DIRECT THROMBIN INHIBITORS:DIRECT THROMBIN INHIBITORS: as replacement of UFH or LWM for heparin-induced thrombocytopenia, or in patients at high-risk of bleeding but low risk of procedural ischemic events GPIIB/IIIA INHIBITORS:GPIIB/IIIA INHIBITORS: routinely in high-risk patients, provisionally in others (abciximab or eptifibatide in the cath lab if immediate [<2.5 h] angio or provisional use; eptifibatide or tirofiban if early [<48 h] angio) LOW MOLECULAR WEIGHT HEPARINLOW MOLECULAR WEIGHT HEPARIN (eg 10 mg/Kg SC enoxaparin twice daily): if invasive strategy is not applicable or deferred UNFRACTIONED HEPARIN:UNFRACTIONED HEPARIN: 50-100 IU/Kg IV bolus and additional doses aiming for target ACT (250–350 s without GpIIb/IIIa inhibitors, and 200–250 with them) if immediate or early invasive strategy

29. Topics Introduction and pathophysiologic insights Antiplatelet regimens Triage to invasive management State of the art PTCA

30. Inferiority of invasive therapy? If PTCA: - routine stenting - bolus + infusion abciximab Medical Rx: - 300 mg aspirin (then >75 mg) - 300 mg clopidogrel (then 75 mg) - 80 mg atorvastatin - 1 mg/Kg enoxaparin

31. Reconciling current evidence

32. Less late PTCA/CABG Improved (long-term) survival But potential increase in peri-procedural infarctions Bavry et al, JACC 2006

33. Invasive vs conservative Rx: impact of stents and antiplatelet treatments

34. Topics Introduction and pathophysiologic insights Antiplatelet regimens Triage to invasive management State of the art PTCA

35. Agostoni et al, JACC 2004 Significantly lower bleedings with radial vs femoral approach PCI (P=0.05), even selecting studies with ACS patients only (N=291) Benefits of the radial approach

36. Burzotta et al, AJC 2003 Benefits of direct stenting 10 trials with 2576 patients randomized to direct stenting (DS) vs conventional stenting (CS) Odds ratio=0.57 (0.35-0.95), P<0.001

37. Lemos et al, JACC 2003 Safety of sirolimus-eluting stents in patients with ACS

38. Moses et al, JACC 2005 Safety of paclitaxel-eluting stents in patients with ACS

39. Urban et al, Circ 2006 Predictors of DES thrombosis

40. Nordmann et al, EHJ 2006 Potential hazards of DES

41. Take home messages

42. Timely triage and administration of standard antithrombotic therapies is pivotal in NSTEACS (ie aspirin, clopidogrel, and heparin [LMW or UFH]) Glycoprotein IIb/IIIa inhibitors can be administered upstream or directly in the cath lab, and are indicated in high-risk patients The role of direct thrombin inhibitors is still to be defined, even if a trade-off between bleeding/peri- procedural MI is likely Default invasive or selectively invasive strategies with ad hoc PTCA are both acceptable, as long as the threshold for medical therapy failure remains low Choice between DES and BMS is best individualized Take home messages

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