Antiplatelet therapy and PCI in unstable angina and NSTEMI

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. 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)

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

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

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 SES BMS Guagliumi et al, Ital Heart J 2003

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

16. 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 Aspirin in unstable angina Wallentin et al, JACC 1991

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

18. LMW heparin in NSTEACS

19. PCI-CURE Substudy 12.6% 1.9% ARR 31% RRR P=0.002 N=2,658 Placebo Clopidogrel 0.15 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

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

21. 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

22. Bivalirudin in ACS: the ACUITY Trial 13,800 pts Endpoint: Death/MI/urgentTVR 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 Bertrand et al, EHJ 2002

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

27. Overwhelming complexity?

28. ESC guidelines: a synthesis • ASPIRIN: 500 mg oral or 300 mg IV loading dose, followed by 75-100 mg daily lifelong • CLOPIDOGREL: 300 to 600 mg loading dose ASAP, followed by 75 mg daily for 9-12 months • 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: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 HEPARIN (eg 10 mg/Kg SC enoxaparin twice daily): if invasive strategy is not applicable or deferred • 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 Bertrand et al, EHJ 2002; Silber et al, EHJ 2005

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

36. 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 Burzotta et al, AJC 2003

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

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

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

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

41. Take home messages

42. Take home messages • 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

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