Gregory Ducrocq Cardiology D epartement Bichat Hospital Paris, France

1. Management of STEMI patients How to implement ESC guidelines Gregory Ducrocq CardiologyDepartement Bichat Hospital Paris, France

3. Whatis the purpose of guidelines? A legal document? Something to follow in any case? Something to learn by heart?

4. « Guidelines summarize and evaluate all availableevidence » « guidelines are not substitutes but are complements for textbooks » « The guidelines do not howeveroverride the responsability of healthprofessionals to makeappropriatedecisionsaccording to the circumstances of individual patient » ESC STEMI guidelines.

5. A summary of availableevidencethatyoushouldimplementaccording to your local conditions

6. How are the guidelines built?

12. Guidelines are not a monolith Still a lot of lowlevelrecommendations A majority of lowlevel of evidence There is room for local interpretation and implementationaccording to your local practice

13. Guidelines Implementation Emergency care Antithrombotictherapy Post discharge

14. A preciseanalysis of local conditions iskey for guidelines implementation

15. Guidelines Implementation Emergency care Antithrombotictherapy Post discharge

17. How do weimplement in France? A network of physician-staffed Mobile Intensive Care Units

18. What are the results?

19. Reperfusion therapy in STEMI FAST MI 2010 registry

20. STEMI: reperfusion therapy IV lysis: 57% prehospital FAST MI 2010 registry

22. Meeting the ESC requirements of the guidelines influences survival Median time from ECG to PCI: 110 min [78; 185] Only 55% met the recommended timelines Adjusted OR: 2.92 (1.17-7.30) P=0.02 FAST MI 2010 registry

23. A preciseanalysis of local conditions iskey for guidelines implementation

24. Implementationaccording to your local conditions? How many PCI capable centers? Which volume? How distant are they? Experience of operators in primary PCI Financial issues: canany patient betreated by primary PCI? Transfer: do you have doctors in the ambulances?

25. Guidelines Implementation Emergency care Antithrombotictherapy Post discharge

26. What do the trials say?

27. Clopidogrel on top of ASA in STEMI 11 10 9 8 7 6 5 4 3 2 1 0 0 7 14 21 28 CLARITY (TIMI 28) COMMIT (CCS-2) N=45,852; 50% lytic,75 mg/day x 16 days N=3491; 75 y/o, lytic, 300 mg load, 75 mg/day, cath in 2-8 days Placebo + ASA: 2310 events (10.1%) 15 Placebo Clopidogrel + ASA 2121 events (9.2%) Clopidogrel 10 Proportion with End Point, % 5 9% proportional risk reduction (P=0.002) Odds ratio 0.80 (95% CI 0.65-0.97) P=0.026 0 0 5 10 15 20 25 30 Day (Up to 28 Days) Day (CV death, recurrent MI, recurrent ischemia) (Death, reinfarction, stroke) Sabatine et al. N Engl J Med.2005 COMMIT Collaborative Group Lancet.2005

28. Clopidogrel non responders Number of patients 112 104 96 n=544 88 80 72 64 56 48 40 32 24 16 8 0 < -20 [-10,0] [11,20] [31,40] [51,60] [71,80] [91,100] Delta 5µM ADP AdaptedfromSerebruany et al. JACC2005

29. Prasugrel New oral antiplatelet agents can achieve faster and stronger platelet inhibition Ticagrelor Brandt et al Am Heart J 2007 Gurbelet al Circulation2009

30. TRITON: Prasugrelvsclopidogrel in ACS 15 138 events Clopidogrel HR 0.81(0.73-0.90)P=0.0004 12.1 CV Death / MI / Stroke 9.9 10 NNT = 46 Prasugrel Endpoint (%) 5 35 events TIMI Major NonCABG Bleeds Prasugrel 2.4 HR 1.32(1.03-1.68)P=0.03 1.8 Clopidogrel 0 NNH = 167 0 30 60 90 180 270 360 450 Days Wiviott S et al NEJM 2007

31. PLATO: ticagrelor vs clopidogrel in ACS Primary endpoint time to CV death, MI or stroke 13 12 11.7 Clopidogrel 11 10 9.8 9 Ticagrelor 8 7 Cumulative incidence (%) 6 5 4 3 2 HR 0.84 (95% CI 0.77–0.92), p=0.0003 1 0 0 60 120 180 240 300 360 Days after randomisation No. at risk Ticagrelor 9,333 8,628 8,460 8,219 6,743 5,161 4,147 Clopidogrel 9,291 8,521 8,362 8,124 6,743 5,096 4,047 Wallentin et al NEJM 2009

32. Time to major bleeding – primary safety event 15 Ticagrelor 11.58 11.20 10 Clopidogrel K-M estimated rate (% per year) 5 HR 1.04 (95% CI 0.95–1.13), p=0.434 0 0 60 120 180 240 300 360 Days from first IP dose No. at risk Ticagrelor 9,235 7,246 6,826 6,545 5,129 3,783 3,433 Clopidogrel 9,186 7,305 6,930 6,670 5,209 3,841 3,479

33. 7 6 Clopidogrel (300 or 600) 5.1 5 4.0 4 Ticagrelor Cumulative incidence (%) 3 2 1 HR 0.79 (95% CI 0.69–0.91), p=0.001 0 0 60 120 180 240 300 360 Days after randomisation 9,333 8,294 8,822 8,626 7119 5,482 4,419 9,291 8,865 8,780 8,589 7079 5,441 4,364 Cardiovascular death over time Wallentin et al NEJM 2009

34. Prasugrel or ticagrelor in STEMI patients?

35. Antithrombotictherapy: What do the Guidelines say?

37. Prasugrel in ACS Pro • Efficacybenefit • 1 / day • Possible greaterefficacy and safety in diabetic patients Against • No cross over withclopidogrel • Cost • Restrictions • < 65 kg • > 75 yo • Previous stroke

38. Ticagrelor in ACS Pro • Efficacybenefit • Mortalitybenefit • Simplification (relative) • Reversibility (relative) Against • Bid • Extra-platelet effects • Bradycardia • Dyspnea • Cost

39. Prasugrel vs. Ticagrelor: Weighingpros and cons in orderto buildyourownalgorithm As simple as possible!

40. Which anticoagulant in primary PCI?

42. Antithromboticsin STEMI The Bichat formulary STEMI – Primary PCI • Aspirine • Load 500 mg • Maintenance 75 mg/j • Ticagrelor • Load 180 mg • Maintenance 90 mg bid • Bivalirudin(prolonged 4 h post PCI) • Abciximab for bailout If bleedingrisk or CI to ticagrelor or association to OAC: Clopidogrel 600/75

43. Guidelines Implementation Emergency care Antithrombotictherapy Post discharge

49. Impact of combinedsecondarypreventiontherapyaftermyocardialinfarction in USIC 2000 Danchin N et al. Am Heart J 2005

50. How to implement?