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“La preparazione alla PTCA nelle SCA”

“La preparazione alla PTCA nelle SCA”. Roma 20 Marzo 2010. Preparazione farmacologica alla PTCA: dalle linee guida ai dati degli studi e dei registri Negli Ospedali con emodinamica. Gavino Casu Cardiologia-Nuoro. Hospital Mortality. 10 8 6 4 2 0. Death in hospital. STEMI. NSTEMI.

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“La preparazione alla PTCA nelle SCA”

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  1. “La preparazione alla PTCA nelle SCA” Roma 20 Marzo 2010 Preparazione farmacologica alla PTCA: dalle linee guida ai dati degli studi e dei registri Negli Ospedali con emodinamica Gavino Casu Cardiologia-Nuoro.

  2. Hospital Mortality 10 8 6 4 2 0 Death in hospital STEMI NSTEMI UA % dead ‘60 25-30% Mid 1980 16% 0 1 2 3 4 5 6 7 8 9 10 Days 4-6% Armstrong. JAMA 2007 ASSENT -4 PCI study. Lancet 2006 GRACE Study. BMJ 2006

  3. PCI –capable Hospital Primary PCI Rescue PCI

  4. Mortality benefit from primary PCI Risk profile Time (PCI-related delay time)

  5. Improve myocardial reperfusion 1)   A shorter delay for access to hospital care (Call-to-door time) 2)   Hospitals capable of performing primary PCI 24/7 3)   Experienced teams capable of using the latest techniques such as thrombus extraction, and optimal antiplatelet and antithombotic therapy Jean Fajadet

  6. re-occlusion, distal embolization, stent thrombosis In-ospital bleeding

  7. Antithrombotic Options

  8. Adjuctive antithrombotic Treatment “ASPIRIN” - Aspirin should be given to all patients with STEMI as soon as possible IB Started dose 150-325 mg in chewable form/250-500 mg iv. A lower dose (75-160 mg) is given orally daily thereafter for life.

  9. Adjuctive antithrombotic Treatment Use of Thienopyridines in Percutaneous Coronary Intervention • preventing post-PCI-related complications; • preventing coronary stent subacute thrombosis; • preventing thrombotic events in native coronary vessels.

  10. Adjuctive antithrombotic Treatment Thienopyrydines:“CLOPIDOGREL” - Clopidogrel should be given as soon as possible to all patients with STEMI undergoing PCI IC Loading dose 300/600 mg. Daily dose of 75 mg

  11. Primary outcome of cardiovascular death, MI, or urgent target-vessel revascularization at 30 days after percutaneous coronary intervention and clopidogrel. 0,8 0,6 0,4 0,2 0 placebo clopidogrel Cumulative hazard rates P=0,03 0 5 10 15 20 25 30 The PCI-CURE trial. Mehta SR et al Days of folllow-up

  12. The PCI-CLARITY trial Major cardiovascular outcomes No. % Outcome Clopidogrel pretreatment No pretreatment Adjusted odds ratio p-value (n=933) (n=930) (95% CI) Outcomes before PCI 37 (4) 58 (6,2) 0,62 (0,40-0,95) 0,03 Sabatine. CLARITY Study. N. Engl J Med 2005 Sabatine. PCI CLARITY. JAMA 2005

  13. Effect of Pretreatment With Clopidogrel on Early Reperfusion and Adverse Event Rates in Univariate-Weighted Logistic Regression Analysis Vlaar. Circulation. 2008

  14. Clopidogrel loading dose 300 vs 600 mg 100 Ticlopidine 2x 500mg, then 250mg BID Clopidogrel 300mg, then 75mg QDClopidogrel 600mg, then 75mg BID 60 % of 20µM ADP-induced aggregation 20 0 0 4 24 48 Time after Administration (hours) Muller I et al. Heart 2001;85:92-93

  15. CURRENT-OASIS 7: a randomized, 2 x 2 factorial trial evaluating optimal dosing strategies for clopidogrel and aspirin in patients with ST and non-ST-elevation acute coronary syndromes managed with an early invasive strategy.

  16. CURRENT OASIS-7 Benefit to doubling clopidogrel dose in ACS patients undergoing PCI Clopidogrel 300/75 mg 600/150mg -15% cardiovascular, death, MI, stroke -22% risk of MI -42% risk stent thrombosis ESC 2009

  17. Double vs standard dose of clopidogrel: Primary outcome and components Mehta S. European Society of Cardiology 2009 Congress; August 30, 2009; Barcelona, Spain.

  18. Double vs standard dose of clopidogrel: Primary outcome and components Mehta S. European Society of Cardiology 2009 Congress; August 30, 2009; Barcelona, Spain.

  19. Bleeding outcome and stent thrombosis in PCI population Mehta S. European Society of Cardiology 2009 Congress; August 30, 2009; Barcelona, Spain.

  20. Results of the aspirin dose comparison: Efficacy and bleeding Mehta S. European Society of Cardiology 2009 Congress; August 30, 2009; Barcelona, Spain.

  21. Clopidogrel limitations • Slow onset • Low level of inhibition • Too much variability

  22. Prasugrel

  23. 15 12.1 Clopidogrel 9.9 10 P<0.001 Prasugrel CV Death, MI, Stroke (%) 5 HR 0.81 (0.73-0.90) NNT= 46 0 0 30 60 90 180 270 360 450 Days Wiviott et al. New Engl J Med 2007;357:2001-2015 TRITON-TIMI 38 • TRITON allowed recruitment of STEMI patients undergoing primary PCI when they presented < 12 hours of symptom onset or secondary PCI when they presented late

  24. Clopidogrel Prasugrel 15 12.4 p=0.02 RRR=21% 10.0 10 9.5 p=0.002 RRR=32% Proportion of patients (%) 6.5 5 HR=0.79 (0.65–0.97) NNT=42 0 Age-adjusted HR=0.81 (0.66-0.99) 0 50 100 150 200 250 300 350 400 450 Time (Days) Primary EP (CV death, MI andstrokeat 15 months) Montalescot Lancet 2009

  25. Clopidogrel Prasugrel 10 8.8 p=0.02 RRR=25% 6.7 5 Proportion of patients (%) HR=0.75 (0.59–0.96) NNT=48 Age-adjusted HR=0.77 (0.60-0.97) 0 0 5 10 15 25 25 30 Time (Days) Keysecondary EP (CV death, MI, and UTVR at 30 days) Montalescot Lancet 2009

  26. Clopidogrel Prasugrel 3 2.8 2.4 2 p=0.008 RRR=51% 1.6 Proportion of patients (%) 1.2 1 0 0 100 200 300 400 Time (Days) StentthrombosisARC Definite/probable p=0.02 RRR=42% HR=0.58 (0.36–0.93) NNT=83 Age-adjusted HR=0.59 (0.37-0.96) Montalescot Lancet 2009

  27. Clopidogrel Prasugrel 2.5 2.4 2.0 1,8 1.5 1.0 Proportion of patients (%) 0.5 0 0 100 200 300 400 Time (Days) Montalescot et al. ESC 2008 TIMI major non-CABG bleeding HR=1.11 (0.70–1.77) NNH=333 Age-adjusted HR=1.19 (0.75-1.89)

  28. ConclusionsIn STEMI patientsundergoing PCI • Prasugrel was superior to standard dose clopidogrel to prevent ischaemic events • Prasugrel did not have more bleeding events compared to those who were treated with clopidogrel, and this was equally true for: • Primary PCI • Secondary PCI • Major bleeding • Minor bleeding • These data make prasugrel an especially attractive alternative to clopidogrel in PCI for STEMI

  29. Non-Thienopyridines , reversible P2Y12 inhibitors Cangrelor Ticagrelor CHAMPION program study PLATO 14.000 pts 18.000 pts Lack of efficacy

  30. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study 13 12 10.65 Clopidogrel 11 10 8,95 9 Ticagrelor 8 7 Cumulative incidence (%) 6 5 4 3 Cardiovascular death, myocardial infarction, stroke 2 1 0 0 60 120 180 240 300 360 Days after randomisation PLATO investigator. Lancet 2010

  31. PLATO 15 Ticagrelor 11.6 11.5 10 Clopidogrel K-M estimated rate (% per year) 5 Time of total major bleeding 0 0 60 120 180 240 300 360 Time after randomizzation (days) PLATO investigator. Lancet 2010

  32. GIIb/IIIa inhibitors Death, MI, TVR (%) IIaA

  33. Periprocedural administration of abiciximab Better myocardial perfusion Neumann.Circulation 1998

  34. 30-day FU 7 Studies 6-12 months FU 6 Studies Abiciximab 30 day FU 5 Studies Small molecules 30-day FU 4 Studies 30-day FU 6 Studies De luca. JAMA 2005

  35. TIROFIBAN In On-TIME 2 trial pre-hospital initiation of high-bolus dose tirofiban in association with aspirin, clopidogrel (600 mg) and heparin improved ST-segment resolution but was not associated with more patency of the infarct vessel or a significant net clinical benefit when compared wit placebo. IIbB Van’t Hof. Lancet 2008

  36. Heparin i.v. bolus 100 U/kg weigt (60 UI/kg is GPIIb/IIIa antagonist are used) IC ACT 250-300 s (200-250 if GPIIb/IIIa)

  37. Percutaneous Coronary Intervention in Patients Receiving Enoxaparin or Unfractionated Heparin After Fibrinolytic Therapy for ST-Segment Elevation Myocardial Infarction in the ExTRACT-TIMI 25 Trial 15 10 5 0 13,8% 10,7% Death or MI (%) Death or recurrent MI 0 120 240 360 480 600 720 Hours ENOX UFH Gibson JACC 2007

  38. A potential role of Enoxaparin STUDY N DOSE Labeque 143 0,5mg/kg IV 1,0 mg/kg SC SWEDES 205 0,75mg/kg IV - WEST 304 1,0 mg/kg SC - 1,0 mg/kg SC 0,3-0,5 mg/kg IV Christy.J Invasiv Cardiol 2008

  39. Bivaluridin Direct thrombin inhibitor Clot-bound Fluid-phase Does not activate platelets

  40. HORIZON-AMI Control (heparin plus GPI) 22 20 18 16 14 12 10 8 6 4 2 0 Bivaluridin 18,3% 15,6% NACE (%) NACE: major bleeding or composite major adverse cardiovascular events 0 1 2 3 4 5 6 7 8 9 10 11 12 Time (month) Mehran. HORIZON-AMI Trial. Lancet 2009

  41. 12 11 10 9 8 7 6 5 4 3 2 1 0 9,2% Control Major bleeding events 5,8% Bivaluridin 0 1 2 3 4 5 6 7 8 9 10 11 12 11,9 12 11 10 9 8 7 6 5 4 3 2 1 0 11,9 MACE (%) MACE: death, reinfarction, target vessel revaculariisation or stroke 0 1 2 3 4 5 6 7 8 9 10 11 12 Mehran. HORIZON-AMI Trial. Lancet 2009

  42. HORIZON-AMI 6 5 4 3 2 1 0 Control 4,8% Bivaluridin 3,5% All-cause mortality (%) 0 1 2 3 4 5 6 7 8 9 10 11 12 Mehran. HORIZON-AMI Trial. Lancet 2009

  43. So……. • Heparin • GIIb/IIIa inhibitors • Aspirin • Loading dose of Clopidogrel • LMWH? • GIIb/IIIa inhibitors • Aspirin • Loading dose of Clopidogrel Abiciximab provides an additional benefit to STEMI patients who receive an optimal Clopidogrel treatment prior PCI? Bivaluridin can replace the use of GIIb/IIIa! So GIIb/IIIa could be used as the bail-out strategy Prasugrel Ticagrelor

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