COME OTTIMIZZARE IL RISULTATO DELLA PCI PRIMARIA NELLO STEMI. Resp. U.O. Cardiologia Magenta

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1 Il continuum della cardiopatia ischemica dalla prevenzione primaria alla manifestazione acuta fino alla fase cronica tardiva Genova 6/7 dicembre 2013 COME OTTIMIZZARE IL RISULTATO DELLA PCI PRIMARIA NELLO STEMI Maurizio D Urbano Resp. U.O. Cardiologia Magenta

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4 ESC guidelines: Coronary heart disease is a chronic condition and patients who have recovered from a STEMI are at high risk for new events and premature death. Most patients with STEMI who die do so after discharge Several intervention can improve prognosis

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7 CADILLAC Study in 2082 pts 49% multi-vessel disease Sorajja et al. European Heart Journal 2007; 28: 1709

8 Long-term mortality

9 STA\ 10 8 DEATH RATE 7,4 6 4 P=0.04 3,3 4,3 3,7 5,6 2 1, MONTHS 24 MONTHS 48 MONTHS CULPRIT ONLY N=538 STAGED MV PCI * N=538 *within 60 days

10 Single PCI Staged PCI

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13 SDO nazionali Composizione della mortalitàper IMA a 30 gg, 60 gg e 1 anno 30 giorni 60 giorni 1 anno Deceduti durante il ricovero indice Dimessi vivi e deceduti nei giorni successivi

14 Cause legate alla procedura (ppci - stent) Cause legate al paziente (stile di vita, fattori di rischio)

15 Limiti più importanti del clopidogrel 1) Ampia variabilità tra pazienti per quanto riguarda la sensibilità a causa di fattori genetici, clinici, ambientali e cellulari 2) Ridotto grado di inibizione piastrinica a causa della ridotta biodisponibilità (il 85% del clopidogrel viene inattivato dalle esterasi nell intestino tenue) 3) Lentezza dell onset e offset d azione a causa del metabolismo pre-epatico ed epatico (pro-farmaco) e del legame irreversibile al recettore dell ADP 4) Risposta limitata nei pazienti STEMI sottoposti a PCI primaria a causa della ridotta biodisponibilità

16 Daemen et al, Lancet 2007

17 Lagerqvist et al, Circulation Int 2009

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20 5 DEFINITE or PROBABLE STENT THROMBOSIS IN STEMI PATIENTS 4 P=0.05 P=0.02 3,4 3 2,8 2,6 NEW DRUG 2 1,6 CLOPIDOGREL 1 0 TRITON PLATO

21 Potent Inhibition of Platelet Activation and Stent Thrombosis: Prasugrel and Ticagrelor Endpoin nt (%) Any Stent at Index PCI N= 12,844 Definite/Probable Stent Thrombosis Prasugrel HR 0.48 P < NNT= 77 Clopidogrel 2.4 (142) Ticagrelor HR 0.72 P=0.01 NNT= 163 Prasugrel 1.1 (68) HR 0.48 P < NNT= Days

22 Definite Stent Thrombosis in 4 Groups (Angiographically Proven) C Standard, A Low Cumulative Hazard Standa rd Clop High ASA Doubl e Clop HR P P Int n Low ASA C Standard, A High C Double, A Low C Double, A High Days

23 Stent thrombosis in diabetic subgroup at study end UA/NSTEMI: p = STEMI: p = All ACS: p = 0.040

24 Patients With Diabetes vs Patients Without Diabetes: Stent Thrombosis (ARC Definite or Probable) TRITON TIMI 38 Stent Th hrombosis (%) HR 0.52 ( ) P = Clopidogrel Prasugrel HR 0.45 ( ) P < Clopidogrel DM Days Wiviott SD et al. Circulation 2008;118: Days Prasugrel No DM P interaction = Cumulative Kaplan-Meier estimates of the rates of key study end points during the follow-up period. ARC=Academic Research Consortium; DM=Diabetes Mellitus; HR=Hazard Ratio 0.9

25 Efficacy of New Drugs/Approaches in Reducing Adverse Outcomes in Diabetes Mellitus From Large-Scale Clinical Trials Study % of Events Hazard Ratio (95% confidence interval) Standard New Drug/Approach TRITON-TIMI ( ) PATIENTS PLATO ( ) PATIENTS CURRENT OASIS ( ) (PCI Cohort) New Drug/Approach Better Standard Clopidogrel Better CURRENT-OASIS= Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events Optimal Antiplatelet Strategy for Interventions; PCI=percutaneous intervention; PLATO= A Study of Platelet Inhibition and Patient Outcomes; TRITON- TIMI= Trial To Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis in Myocardial Infarction. Reprinted with permission from Ferreiro JL, Angiolillo DJ. Circulation :

26 Lifestyle interventions and risk factor control

27 Prog Cardiovasc Dis May-Jun;45(6): Hospital- and clinic-based smoking cessation interventions for smokers with cardiovascular disease. Smoking cessation after myocardial infarction reduces subsequent cardiovascular mortality by nearly 50%. the use of effective strategies to reduce the prevalence of tobacco use is a high priority

28 Weight control

29 Blood pressure control From PROVE IT TIMI 22: after ACS systolic pressure < 140 but not <110 Recommended Pharmacotherapy after STEMI: betablockers, ACE inhibitors or ARBs Reduction of salt intake, increased phisical activity, weight loss

30 Lipid lowering therapy after ACS A-to-Z vs. MIRACL & PROVE-IT Different patient populations MIRACL PROVE-IT A-to to-z % pts per ACS type UA :46 n-stemi:54 UA:33 N-STEMI:33 STEMI:33 UA:16,8 n-stemi:43,2 STEMI:40 % diabetic pts % pts treated with PCI: Therapy initiation (gg) (median:7) 5 (median median: ) ua= Unstable Angina n-stemi STEMI= non ST-Elevation Myocardial Infarction STEMI= ST -Elevation Myocardial Infarction

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32 RIDUZIONE SIGNIFICATIVA DEL 16% NEL RISCHIO DI MORTE CORONARICA O INFARTO MIOCARDICO Cannon CP et al, J Am Coll Card, 48 (3): , 2006

33 EFFETTI PLEIOTROPICI DELLE STATINE Effetti antiaterosclerotici su: Disfunzione dell endotelio Infiammazione (inibizione delle molecole di adesione) Stabilità della placca (inibizione di MMP ) Ossidazione e densità LDL Proliferazione SMC Esterificazione e accumulo di colesterolo Effetti Antitrombotici su: Fattore tissutale Aggregazione piastrinica Viscosità ematica e fibrinogeno Fibrinolisi Corsini, Int J Clin Prat

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35 ESC 2012 Linee guida STEMI

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38 Brusseau, NEJM 2004

39 Prevalenza di Diabete nelle SCA Dati dei Registri 60 % Euro Heart Survey (ACS pts) Eur Heart J 2004 CRUSADE (NSTEMI pts) JAMA 2004 NRMI (STEMI pts) Arch Intern Med 2005 NRMI (NSTEMI pts) Arch Intern Med 2005

40 1-year mortality % % No DM DM 0 Oral Rx Insulin Van der Schaaf RJ et al. Heart 2006

41 Diabetic Subgroup N= PATIENTS Clopidogrel 17.0 Endpo oint (%) CV Death / MI / Stroke Prasugrel 12.2 HR 0.70 P<0.001 NNT = TIMI Major NonCABG Bleeds Clopidogrel 2.6 Prasugrel Days Wiviott, Braunwald, Angiolillo et al Circulation 2008

42 impact of glucose lowering treatment on prognosis in diabetic patients with ami European Heart Journal (2008) 29,

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49 Stent thrombosis HR for Ticagrelor Clopidogrel ticagrelor p (n=6,732) (n=6,676) (95% CI) value* Stent thrombosis, % Definite ( ) Probable or definite ( ) 0.01 Possible, probable, or definite ( ) 0.003

50 TRITON TIMI-38 STEMI Cohort N= CV Death / MI / Stroke Clopidogrel 12.4% Perce ent (%) % 6.5% HR 0.68 ( ) P=0.002 TIMI Major NonCABG Bleeds Prasugrel 10.0% HR 0.79 ( ) P=0.02 NNT = 42 Prasugrel 2.4 Clopidogrel Days From Randomization Montalescot et al Lancet 2008.Adapted with permission from Antman EM. 50

51 ACC/AHA Guidelines for PCI JACC 2006; 47: 216 ESC Guidelines for STEMI EHJ 2008; 29: 2917

52 4024 STEMI Patients with Multivessel CAD 12,5% 22,7% 64,8% CULPRIT ONLY MV P-PCI Staged Procedures* * Within 60 days

53 10 8 DEATH RATE 7,2 6 4 P=0.04 2,4 4,2 5,8 4,9 2 0,9 0 IN-HOSPITAL 12 MONTHS 24 MONTHS CULPRIT ONLY N=503 MV PCI during Primary PCI N=503

54 Landmark Analysis of Time From First Event to Cardiovascular Death By Randomized Therapy 7.1% Clopidogrel Prasugrel HR % CI: 0.25, 0.82 p= % Days from first event to CV death or last follow-up Number at risk Prasugrel Clopidogrel Murphy SA, et al. Eur Heart J 2008;29(20):

55 Clopidogrel: Double vs Standard Dose Primary Outcome: PCI Patients CV Death, MI or Stroke Clopidogrel Standard Cumulative Ha azard Clopidogrel Double HR % CI P= % RRR Days

56 Recommendations for the use of Thienopyridines in STEMI

57 Eventi cardiaci avversi maggiori a 30 giorni nel trattamento con statine ad alte dosi vs. bracci di controllo Patti G et al. Circulation 2011;123:

58 Un-adjusted 1-year survival for 130,099 elderly patients after myocardial infarction by initial serum creatinine levels and creatinine clearance tertiles (Cockroft-Gault) CIC CURIAMO INSIEME IL CUORE Shlipak MG. et al. Ann Intern Med 2002

59 MB 2-3 MB 0-1

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62 CKD pts treated with clopidogrel CKD pts treated with ticagrelor

63 GRACE ACS Risk model Ischemic risk O,8-1,19 I (no CHF) 6% 14% 21% 37%

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68 Efficacy in reducing adverse outcomes of new drugs and approaches tested in large-scale clinical trials in diabetes mellitus (DM) patients. Ferreiro J L, and Angiolillo D J Circulation 2011;123: Copyright American Heart Association

69 Conclusions The outcome of ACS patients has significantly improved over the recent years, thanks to the increased use of invasive strategies and of effective pharmacological treatments. In particular, new antithrombotic agents with acceptable bleeding risk have further contributed to improved survival of such patients.