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Giuseppe Biondi Zoccai University of Turin , Turin , Italy METCARDIO, Turin , Italy

THE IMPORTANCE OF AN ADEQUATE RISK-BENEFIT RATIO IN THE ANTIPLATELET TREATMENT OF ACS PATIENTS. Giuseppe Biondi Zoccai University of Turin , Turin , Italy METCARDIO, Turin , Italy gbiondizoccai@gmail.com.

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Giuseppe Biondi Zoccai University of Turin , Turin , Italy METCARDIO, Turin , Italy

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  1. THE IMPORTANCE OF AN ADEQUATE RISK-BENEFIT RATIO IN THE ANTIPLATELET TREATMENT OF ACS PATIENTS Giuseppe Biondi Zoccai UniversityofTurin, Turin, Italy METCARDIO, Turin, Italy gbiondizoccai@gmail.com BMS & SanofiAventisSponsored Symposium: State of art of dual antiplatelet therapy in ACS Bologna, 25/9/2008 – 13.05-13.25

  2. SCOPE OF THE PROBLEM Bleeding Thromboticevents

  3. SCOPE OF THE PROBLEM Bleeding Thromboticevents

  4. SCOPE OF THE PROBLEM

  5. LEARNING GOALS • What is the risk and the impact of atherothrombotic events in ACS? • What is the risk and the impact of bleeding events in ACS? • How can we strike a balance between risk and benefit of antiplatelet therapy in ACS?

  6. LEARNING GOALS • What is the risk and the impact of atherothrombotic events in ACS? • What is the risk and the impact of bleeding events in ACS? • How can we strike a balance between risk and benefit of antiplatelet therapy in ACS?

  7. IN OTHER WORDS… WHAT ELSE SHOULD I EXPECT FROM ATHEROTHROMBOSIS AFTER THE INDEX EVENT?

  8. WHAT IS THE CLINICAL BURDEN OF ATHEROTHROMBOSIS? DEATH STROKE MI TVR RE-HOSPITALIZATION My main tool to avoid athero-thrombosis: antithrombotic Rx

  9. ATHEROTHROMBOTIC EVENTS AFTER ADMISSION FOR AMI Capewell et al,Heart 2006

  10. ATHEROTHROMBOTIC EVENTS AFTER ADMISSION FOR UA Capewell et al,Heart 2006 Capewell et al, Heart 2006

  11. PREDICTORS OF ATHERO-THROMBOTIC EVENTS: TIMI Score (n=7081) * * all-cause mortality, myocardial infarction, and severe recurrent ischemia prompting urgent revascularization Antman et al, JAMA 2000;284:835-42

  12. EXTREMELY VARIABLE PATHOPHYSIOLOGY 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)

  13. EXTREMELY VARIABLE IMPACT OF MYOCARDIAL INFARCTION: case study from the PURSUIT trial Akkerhuis et al, Circulation 2002;105:554-556

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

  15. VARIABILITY IN CLOPIDOGREL 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. LEARNING GOALS • What is the risk and the impact of atherothrombotic events in ACS? • What is the risk and the impact of bleeding events in ACS? • How can we strike a balance between risk and benefit of antiplatelet therapy in ACS?

  17. IN OTHER WORDS…WHEN IS MUCH TOO MUCH?

  18. THE CASE FOR FOCUSING ON BLEEDING • It is common • It is expensive • Patients remember bleeding events more than asymptomatic enzyme leaks • It is associated with increased mortality

  19. THE CASE FOR FOCUSING ON BLEEDING • It is common • It is expensive • Patients remember bleeding events more than asymptomatic enzyme leaks • It is associated with increased mortality • Strategies that prevent or reduce bleeding may reduce mortality

  20. THE CASE FOR FOCUSING ON BLEEDING • It is common • It is expensive • Patients remember bleeding events more than asymptomatic enzyme leaks • It is associated with increased mortality • Strategies that prevent or reduce bleeding may reduce mortality • Minimizing bleeding should be an essential part of modern therapy of CAD

  21. PREVALENCE OF MAJOR BLEEDING: GRACE Registry (n=24045) Moscucci et al, Eur Heart J 2003;24:1815-1823

  22. PREDICTORS OF MAJOR BLEEDING: GRACE Registry (n=24045) Moscucci et al, Eur Heart J 2003;24:1815-1823

  23. IMPACT* ON MORTALITY OF BLEEDING IN ACS P=0.20 P<0.0001 P<0.0001 Survival *at both univariate and multivariable analyses Rao et al, Am J Cardio 2005;96:1200-1206

  24. SIMILAR PREDICTORS AND IMPACT* FOR BLOOD TRANSFUSIONS IN AMI *at both univariate and multivariable analyses Aronson et al, Am J Cardiol 2008;102:115-119

  25. IMPACT ON COSTS: case study from the REPLACE-2 trial Cohen et al, J Am Coll Cardio 2004;44:1792-1800

  26. LEARNING GOALS • What is the risk and the impact of atherothrombotic events in ACS? • What is the risk and the impact of bleeding events in ACS? • How can we strike a balance between risk and benefit of antiplatelet therapy in ACS?

  27. OVERWHELMING COMPLEXITY?

  28. FINDING THE BALANCE: AN EASY CASE

  29. FINDING THE BALANCE: ANOTHER EASY CASE

  30. WHAT ABOUT TOUGHER CASES?

  31. RATIONALE FOR QUADRUPLE END-POINT IN PCI Ndrepepa et al, J Am Coll Cardiol 2008;51:690-7

  32. RATIONALE FOR QUADRUPLE END-POINT IN PCI Ndrepepa et al, J Am Coll Cardiol 2008;51:690-7

  33. DEFINITION OF NET ADVERSE CLINICAL EVENTS (NACE) ALL CAN IMPACT ON PROGNOSIS, SYMPTOMS, AND COSTS! BUT EACH MAY IMPACT THESE IN DIFFERENT DIRECTIONS MAJOR BLEEDING DEATH PCI/ CABG MI STROKE Ndrepepa et al, J Am Coll Cardiol 2008;51:690-7

  34. DEFINITION OF NET ADVERSE CLINICAL EVENTS (NACE) ALL CAN IMPACT ON PROGNOSIS, SYMPTOMS, AND COSTS! BUT EACH MAY IMPACT THESE IN DIFFERENT DIRECTIONS MAJOR BLEEDING DEATH NACE: composite ofall cause death, non-fatalmyocardialinfarction, non-fatalstroke, PCI/CABG, and non-fatal major bleeding* PCI/ CABG MI STROKE *in several cases, stroke is not included in NACE definition

  35. WHAT ABOUT CLOPIDOGREL IN REAL LIFE ? Alexander et al, Am Heart J 2008;156:606-612

  36. SUMMARY OF EVIDENCE ON CLOPIDOGREL LOADING

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

  38. DO-IT-YOURSELF ANTIPLATELET THERAPY?

  39. DO-IT-YOURSELF ANTIPLATELET THERAPY! Bonello et al, J Am Coll Cardiol 2008;51:1404-11

  40. DO-IT-YOURSELF ANTIPLATELET THERAPY! 26 patients receiving 4 600 mg loading doses of clopidogrel 24 hours apart (2.4 g)! Bonello et al, J Am Coll Cardiol 2008;51:1404-11

  41. A GLIMPSE AT THE FUTURE

  42. TAKE HOME MESSAGES

  43. 1. A COMPREHENSIVE APPRAISAL OF THROMBOTIC & BLEEDING RISKS IS NEEDED IN PATIENTS WITH ACS THROMBOSIS BLEEDING

  44. 2. BETTER YET PRACTICAL RISK-STRATIFICATION TOOLS FOR BLEEDS AND THROMBOSES ARE WARRANTED

  45. 3. EVERY PATIENT WILL HAVE AN INDIVIDUALIZED TREATMENT, DEPENDING ON OVERALL RISK PROFILE AND ACUITY

  46. For further slides on these topics please feel free to visit the metcardio.org website:http://www.metcardio.org/slides.html

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