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Dott. Antonio Butera Lamezia Terme

Dott. Antonio Butera Lamezia Terme. U. O. CARDIOLOGIA con UTIC. Lamezia. Terme. Preparazione farmacologica alla PTCA: STEMI Negli ospedali senza emodinamica. Roma, 20 marzo 2010. 1. 2. 2009. Facilitaded and Rescue PCI…non longer used…potentially misleading labels.

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Dott. Antonio Butera Lamezia Terme

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  1. Dott. Antonio Butera Lamezia Terme U. O. CARDIOLOGIA con UTIC Lamezia Terme Preparazione farmacologica alla PTCA: STEMI Negli ospedali senza emodinamica Roma, 20 marzo 2010

  2. 1 2

  3. 2009 • Facilitaded and Rescue PCI…non longer used…potentially misleading labels

  4. Scopi del trattamento farmacologico pre PTCA • Limitazione di eventi e riduzione del danno ischemico pre-PCI • “Facilitazione” dell’angioplastica • Riduzione delle complicanze peri e post-procedurali (trombosi dello stent, ischemia) • (Il tutto con minori effetti pro-emorragici) -I sanguinamenti maggiori moltiplicano MACE: “GRACE” EHJ 2003; Eikelboom JW et al: Circulation 2006; Nikolski E et al: EHJ 2007; “CRUSADE “ Circulation 2009-

  5. Facilitata

  6. Razionale dell’Angioplastica facilitata • La maggiore pervietà dell’IRA prima dell’angioplastica migliora l’outcome 6 months mortality TIMI 3 (n=375) 100% 98% 96% 94% 92% 90% 0.5% TIMI 2 (n=295) 2.8% Survival (%) TIMI 0/1 (n=1,657) 4.4% log-rank p for trend = 0.009 0 1 2 3 4 5 6 Stone GW Circulation 2001;104:636 Months

  7. IMA ST (< 6h) ASSENT- 4 PCI: study design n = 2000 n = 2000 ASA + UFH (bolus 40U/kg) + TNK-tPA ASA + UFH (bolus 70u/Kg) Immediate PTCA Immediate PTCA Stent or clopidogrel at researcher’s discretion No anti-GP IIb/IIIa Stent, clopidogrel or anti-GP IIb/IIIa at researcher’s discretion Primary endpoints: death, heart failure or cardiogenic shock at 90 days Lancet 2006

  8. ASSENT- 4 PCI Trial: TIMI Flow Grade TIMI grade 3 flow prior to PCI and TIMI grade 2/3 flow post-PCI (%) p=0.03 • TIMI grade 3 flow prior to PCI was present more frequently in the TNK + PCI arm (43.6% vs 15.0%) • TIMI grade 2/3 post-PCI was slightly higher in the PCI alone group (95.3% vs 97.6%) p<0.001 Lancet 2006

  9. ASSENT-4: Primary Endpointmortality, CHF, Shock at 90 days p=0.04 Lancet 2006

  10. ASSENT-4 PCI : in-hospital cardiac events Lancet 2006

  11. ASSENT-4 PCI: in-hospital stroke rates van de Werf F. European Society of Cardiology Congress 2005;September 4-7, 2005; Stockholm, Sweden. Lancet 2006

  12. Conclusioni ASSENT - 4

  13. Major Objectives ? Abciximab Facilitated Primary PCI ? 2°: To test if Reteplase/Abciximab is superior to facilitation with Abciximab aloneTo test if Abciximab facilitation is superior to Primary PCI with in lab Abciximab 1° - To test if Reteplase/Abciximab Facilitated PCI is superior to Primary PCI with in lab Abciximab Primary end-point:mortality, CHF, VF, Shock at 90 days Primary PCI with in lab Abciximab R ? Reteplase/AbciximabFacilitated Primary PCI NEJM 2008

  14. TIMI Flow in IRA Pre-PCI % Subjects with TIMI 2/3 (Patency) Pre-PCI p < 0.0001 p < 0.0001 61 % Percentage 25 % TIMI 2 TIMI 3 26 % 25 % 11 % 36 % 12 % 15 % 13 % Abciximab Facilitated PCI (n=809) Primary PCI (in lab Abciximab) (n=790) Reteplase/Abciximab Facilitated PCI (n=815)

  15. Primary Endpoint:mortality, CHF, VF, Shock at 90 days p=0.55

  16. TIMI Major or Minor Bleeding (nonintracranial) through Discharge/Day7 p<0.001 p<0.001 p=0.025 p=0.008 p=0.006 p=0.547 p=0.025 p=0.141 p=0.127

  17. CONCLUSIONI …il rapporto rischio/beneficio della pPCI con Abciximab somministrato direttamente in emodinamica è migliore delle due strategie di facilitazione…

  18. (19 studi)

  19. Ma se la pPCI non si potesse proprio fare….specialmente nei pazienti ad alto rischio…

  20. CARESS Study design STEMI patients <12 hrs from symptom onset Admitted to centres without PCI facilities and at least one high risk feature: >15 mm ST Elevation new onset LBBB, previous MI, Killip Class >2, < 35% LVEF ASA 300-500 mg iv;Reteplase half dose; UFH (40 U/kg -max 3000-; 7 U/kg/h); Abciximab 0.25 mg/kg bolus 0.125 mg/kg/min x 12 h Admit to CCU and only transfer for PCI if persistent ST elevation at 90 min (>50% basal ECG), chest pain or haemodynamic compromise Urgent transfer after lysis to nearest PCI centre for PCI plus stenting Primary outcome: Death, Reinfarction, Refractory Ischemia at 30 Days Lancet 2008

  21. Primary outcome: Death, Reinfarction, Refractory Ischemia at 30 Days

  22. Il beneficio del trasferimento immediato si è ottenuto malgrado 1/3 dei pazienti del braccio di controllo sia stato trattato con la Rescue. Il rischio di sanguinamento non è stato differente nei due Gruppi (e comunque basso: solo 5 ICH nei 598 pz )

  23. ‘High Risk’ ST Elevation MI within 12 hours of symptom onset Community Hospital Emergency Department TNK + ASA + Heparin / Enoxaparin + Clopidogrel “Pharmacoinvasive Strategy” Urgent Transfer to PCI Centre “Standard Treatment” Assess chest pain, STresolution at 60-90 minutes after randomization Failed Reperfusion* Successful Reperfusion PCI Centre Cath Lab Cath / PCI within 6 hrs regardless of reperfusion status Cath and Rescue PCI  GP IIb/IIIa Inhibitor Elective Cath  PCI > 24 hrs later Repatriation of stable patients within 24 hrs of PCI * ST segment resolution < 50% & persistent chest pain, or hemodynamic instability Randomization stratified by age (≤75 vs. > 75) and by enrolling site NEJM 2009

  24. Primary end-point: 30-day composite Death, Reinfarction, recurrent ischemia, CHF, Shock

  25. Conclusioni • In paz con STEMI ad alto rischio sottoposti alla fibrinolisi in centri periferici, il trasferimento entro 6 ore al centro hub per eseguire la PCI si associa ad una riduzione significativa di eventi ischemici, (malgrado il ricorso in circa il 40% dei pazienti alla PCI rescue) • senza incrementare gli eventi emorragici, • La PCI precoce dopo trombolisi, si è dimostrata più “safe” che nei precedenti trials (progressi con gli stent ed altra terapia concomitante –Clopidogrel-?)

  26. 1.Se possibile pPCI 2.Se non possibile pPCI

  27. 2009

  28. Anti IIB/IIIA pre-cathlab • Molti studi eseguiti prima della doppia antiaggregazione non più attuali. • BRAVE-3 (Abciximab): clinicamente neutro; ON-TIME 2 (Tirofiban): clinicamente neutro. • MULTISTRATEGY: Abciximab vs Tirofiban e BMS vs DES (Sirolimus) – vantaggio del DES. • FINESSE: Braccio abciximab clinicamente neutro (con + emorragie rispetto alla somministrazione in emodinamica)

  29. 2009

  30. Come identificare, eventualmente, i pazienti della Classe 2B? Am Heart J 2008

  31. Early abciximab administration before primary percutaneous coronary intervention improves clinical outcome in elderly patients transferred with ST-elevation myocardial infarction: Data from the EUROTRANSFER registry 30-day death + Reinfarction 30-day death % % P = 0.001 P = 0.001 Nessuna differenza per emorragie nel gruppo >/= 65 aa Dziewiers et al: Int J Cardiol 2009

  32. 2009

  33. ISIS-2ISIS-2 (Second International Study of Infarct Survival) Collaborative Group, Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarctions: ISIS-2. Lancet 1988 ii 349-360 -20%

  34. Collaborative meta­analysis of randomised trials ofantiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:71-86 NNT = 26

  35. ACC/AHA Guidelines 2004 (invariate per l’ASA) ESC Guidelines 2008

  36. Biotransformation and Mode of Action of Clopidogrel, Prasugrel, and Ticagrelor Schomig A. N Engl J Med 2009

  37. Medical Rx Group PCI Group 0.20 0.20 Placebo 0.15 0.15 Placebo 0.10 0.10 Clopidogrel 0.05 0.05 RR: 0.72 (0.57-0.90) RR: 0.80 (0.69-0.92) 0.0 0.0 4 100 200 300 4 100 200 300 Il beneficio del Clopidogrel (300>75) è maggiore nei pazienti sottoposti a PCI CURE Primary end-point: CVD+MI+Stroke) CVD/MI/Stroke CVD/MI/Stroke Clopidogrel -30% -19% NEJM 2001

  38. PCI- The CURE Investigators: Lancet 2001

  39. Clarity TIMI 28 (Fibrinolisi) PCI- Clarity TIMI 28 -36% -46% NEJM 2005 JAMA 2005

  40. Meta-Analysis of Clopidogrel Pretreatment Clopidogrel No TrialPretreatmentPretreatment PCI-CURE 3.6 5.1 CREDO n/a n/a PCI-CLARITY 4.0 6.1 Overall 3.7 5.5 Clopidogrel No TrialPretreatmentPretreatment PCI-CURE 2.9 4.4 CREDO 6.0 7.1 PCI-CLARITY 3.3 5.4 Overall 3.9 5.5 MI before PCI (%) Favors Pretreatment Favors No Pretreatment OR 0.67 P=0.005 CVD or MI after PCI (%) 0.25 0.5 1.0 2.0 OR (95% CI) OR 0.71 P=0.004 0.25 0.5 1.0 2.0 OR (95% CI) Sabatine MS et al. JAMA 2005

  41. CURRENT OASIS: Study Design, Flow and Compliance • 25,087 ACS Patients(UA/NSTEMI 70.8%, STEMI 29.2%) • Planned Early (<24 h) Invasive Management with intended PCI • Ischemic ECG Δ (80.8%) or ↑cardiac biomarker (42%) Randomized to receive (2 X 2 factorial): CLOPIDOGREL: Double-dose(600 mg then150 mg/d x 7d then 75 mg/d)vsStandard dose(300 mg then 75 mg/d) ASA: High Dose (300-325 mg/d) vsLow dose(75-100 mg/d) Angio 24,769 (99%) PCI 17,232 (70%) No PCI 7,855 (30%) No Sig. CAD 3,616 CABG 1,809 CAD 2,430 Efficacy Outcomes: CV Death, MI or stroke at day 30 Stent Thrombosis at day 30 Safety Outcomes:Bleeding (CURRENT defined Major/Severe and TIMI Major) Key Subgroup:PCI v No PCI Complete Followup 99.8%

  42. CURRENT OASIS: Double vs Standard Dose Primary Outcome (CV Death, MI or Stroke): PCI Patients Clopidogrel Standard 15% RRR 0.04 Clopidogrel Double 0.03 Cumulative Hazard 0.02 HR 0.85 95% CI 0.74-0.99 P=0.036 0.01 0.0 0 3 6 9 12 15 18 21 24 27 30 Days ESC 2009

  43. CURRENT OASIS 7: Double vs Standard DoseDefinite Stent Thrombosis (Angio confirmed) Clopidogrel Standard Dose 0.012 42% RRR 0.008 Cumulative Hazard Clopidogrel Double Dose 0.004 HR 0.58 95% CI 0.42-0.79 P=0.001 0.0 0 3 6 9 12 15 18 21 24 27 30 Days ESC 2009

  44. Clopidogrel: Double v Standard DosePCI Cohort Subgroups CV Death, MI or Stroke MI or Stent Thrombosis 2N Std % Double % Intxn P Std % Double % Intxn P Overall 17232 4.5 3.9 3.7 3.0 NSTEMI/UA 10886 4.2 3.6 3.6 3.1 0.805 0.248 STEMI 6346 5.0 4.2 4.0 2.8 Male 13009 4.1 3.6 3.5 3.0 0.419 0.148 Female 4223 5.8 4.6 4.6 3.0 Age <= 65 yrs 10975 3.0 2.7 2.9 2.2 0.702 0.418 Age > 65 yrs 6257 7.1 6.0 5.2 4.4 Non-Diabetic 13400 4.2 3.6 3.6 2.8 0.836 0.567 Prev Diabetic 3831 5.6 4.9 4.1 3.6 No Inhosp GPIIb/IIIa 12288 3.9 3.5 3.1 2.5 0.465 0.894 GPIIb in hosp 4936 6.0 4.7 5.2 4.1 No Prot Pump Inhib 7675 3.8 3.2 3.1 2.3 0.408 0.613 Prot Pump Inhib 5557 5.7 4.2 4.8 3.3 Non-smoker 10845 4.9 4.6 3.9 3.5 0.045 0.050 Current Smoker 6380 3.8 2.6 3.4 2.1 ASA Low 8620 4.2 4.3 3.6 3.2 0.024 0.191 ASA High 8612 4.8 3.5 3.8 2.7 Double Dose Better Double Dose Better 0.50 1.50 0.50 1.50

  45. Clopidogrel Double vs Standard DoseBleeding Overall Population

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