La presentazione è in caricamento. Aspetta per favore

La presentazione è in caricamento. Aspetta per favore

LA TERAPIA ANTIAGGREGANTE PRIMA E DOPO STENT Francesco Bellandi U.O. Cardiologia - Ospedale di Prato IL DIVENIRE CLINICO IN CARDIOLOGIA Firenze 31 Ottobre.

Presentazioni simili


Presentazione sul tema: "LA TERAPIA ANTIAGGREGANTE PRIMA E DOPO STENT Francesco Bellandi U.O. Cardiologia - Ospedale di Prato IL DIVENIRE CLINICO IN CARDIOLOGIA Firenze 31 Ottobre."— Transcript della presentazione:

1 LA TERAPIA ANTIAGGREGANTE PRIMA E DOPO STENT Francesco Bellandi U.O. Cardiologia - Ospedale di Prato IL DIVENIRE CLINICO IN CARDIOLOGIA Firenze 31 Ottobre 2008

2 RIDUZIONE DEL RISCHIO DI EVENTI ISCHEMICI POSTPROCEDURALI RIDUZIONE DEL RISCHIO DI TROMBOSI DELLO STENT RISCHIO EMORRAGICO

3 Antiplatelet Therapy Single Antiplatelet Rx Dual Antiplatelet Rx Higher IPA ASA ASA + Clopidogrel ASA + Prasugrel - 22% - 20% - 19% + 60% + 38% + 32% Reduction in Ischemic Events Increase in Major Bleeds ISCHEMIC EVENTS BLEEDINGS

4 Ndrepepa G et al; JACC 2008: Periprocedural Bleeding and 1-Year Outcome After Percutaneous Coronary Interventions OR: 3.7; P < OR: 4.7; P < 0.001

5 ASA TIENOPIRIDINE INIBITORI GLICOPROTEINE DOPPIAANTIAGGREGAZIONEDOPPIAANTIAGGREGAZIONE

6 Antiplatelets treatment Main open issues: Need of pretreatment Loading Dose Length and Dose of long term therapy Clopidogrel low responsiveness Perioperative Management in patients with stents Dual antiplatelet therapy and Chronic oral Anticoagulation

7 Antiplatelets treatment Main open issues: Need of pretreatment Loading Dose Length and Dose of long term therapy Clopidogrel low responsiveness Perioperative Management in patients with stents Dual antiplatelet therapy and Chronic oral Anticoagulation

8 SABATINE MS et al, Am Heart J 2008: MACE a 30 giorni (morte, infarto e stroke) TOTALE 6336 pz Riduzione 29% Dal 5.8% al 4.1% P = 0.004

9 SABATINE MS et al, Am Heart J 2008: TIMI major or minor bleeding TOTALE 6336 pz Dal 1.9% al 2.3% OR: 1,21 P = 0.29

10 Steinhubl S, J Am Coll Cardiol 2006; 47: CREDO Study : Optimal timing for the initiation of pre-treatment with 300mg clopidogrel before PCI.

11 PCI – ESC 2005 Pretrattamento in caso di PCI Dose 300 mg almeno 6 ore prima della PCI programmata per CAD stabile e idealmente il giorno prima Pretrattamento in caso di PCI Dose 300 mg almeno 6 ore prima della PCI programmata per CAD stabile e idealmente il giorno prima

12 Antiplatelets treatment Main open issues: Need of pretreatment Loading Dose Length and Dose of long term therapy Clopidogrel low responsiveness Perioperative Management in patients with stents Dual antiplatelet therapy and Chronic oral Anticoagulation

13 Faster Onset of Action and Higher Level of Platelet Inhibition (Dose-Effect): ALBION Trial Inhibition (%) Shortened time to reach the highest Level of inhibition of the 300 mg LD P < 0.05 vs. 300 mg LD Time (Hours) Maximum Inhibition of Platelet Aggregation (ADP 5 mol/L) 300 mg LD600 mg LD900 mg LD Montalescot G, et al. JACC 2006

14 P = *Death, MI; TVR to 30 d ISAR REACT II: 2022 NSTE ACS pts Kastrati A et at; JAMA 2005

15 ISAR-REACT II Study: Optimal timing for the initiation of pre-treatment with 600 mg clopidogrel before PCI > 3 h 3 h Clopidogrel interval (hours) 19.8% 26.4% 25.1% 30.4% > 3 h 3 h AbciximabPlacebo one - yearDeath/MI/TVR Ndrepepa G, Eur Heart J 2007

16 600 mg300 mg (n = 126)(n = 129) Composite 1° Endpoint (%)* P = *Death, MI; TVR to 30 d ARMYDA–2: Randomized Trial of Clopidogrel Loading Dose 4-8 Hours Before PCI Patti G, et al. Circulation. 2005;111:

17 PCI – ESC 2005 ARMYDA 2 PCI URGENTE o Dose carico 600 mg immediatamente dopo il primo PCI ad hoc per CAD stabile contatto medico, se clinicamente giustificabile PCI URGENTE o Dose carico 600 mg immediatamente dopo il primo PCI ad hoc per CAD stabile contatto medico, se clinicamente giustificabile

18 PCI – AHA 2007 update Classe IIa If clopidogrel is given at the time of procedure, supplementation with GP IIb/IIIa receptor antagonists can be beneficial. If clopidogrel is given at the time of procedure, supplementation with GP IIb/IIIa receptor antagonists can be beneficial. (Level of Evidence: B).

19 Oasis – 7 CURRENT study. Clopidogrel optimal loading dose Usage to Reduce Recurrent EveNTs Randomized, multinational, double-blind, comparing a high loading dose regimen of Clopiodgrel versus standard dose in pts with NSTEMI managed with an early invasive strategy

20 Antiplatelets treatment Main open issues: Need of pretreatment Loading Dose Length and Dose of long term therapy Clopidogrel low responsiveness Perioperative Management in patients with stents Dual antiplatelet therapy and Chronic oral Anticoagulation

21 TROMBOSI DELLO STENT definizione e classificazione acuta PCI24 ore1 mese subacuta 1 anno tardiva (late)very late Classificazione temporale Definizione ARC (Academic Research Consortium) Trombosi definita = sindrome coronarica acuta con evidenza angiografica oTrombosi definita = sindrome coronarica acuta con evidenza angiografica o autoptica di trombosi o occlusione dello stent autoptica di trombosi o occlusione dello stent Trombosi probabile = 1) qualsiasi morte non altrimenti spiegabile entro 30 dallaTrombosi probabile = 1) qualsiasi morte non altrimenti spiegabile entro 30 dalla dalla procedura; dalla procedura; 2) infarto miocardico acuto nel territorio dellarteria coronica 2) infarto miocardico acuto nel territorio dellarteria coronica trattata senza conferma angiografica trattata senza conferma angiografica Trombosi possibile = qualsiasi morte non altrimenti inspiegabile oltre 30 giorni dalla procedura

22 Stent metallici endotelizzazione completata in 9-12 giorni terapia antitrombotica per 3-4 settimane dopo impianto di stent

23 ASAASA + TiclopidinaASA + Warfarin Stent thrombosis STARS 2,9%0,5%2,7% ISAR -0,8%5,4%

24 PCI – AHA 2007 update Classe I For post-PCI patients receiving a BMS, clopidogrel should be given for a minimum of 1 month For post-PCI patients receiving a BMS, clopidogrel should be given for a minimum of 1 month (level of Evidence: A) and ideally up to 12 months (unless the patient is at increased risk of bleeding; then it should be given for a minum of 2 weeks and ideally up to 12 months (unless the patient is at increased risk of bleeding; then it should be given for a minum of 2 weeks (Level of Evidence: B )

25 durata terapia antitrombotica ?Stent medicati azione antiproliferativa endotelizzazione ritardata durata terapia antitrombotica ?

26 TROMBOSI DELLO STENT QUALE LA DIMENSIONE DELPROBLEMA? NEI VARI TRIALS RANDOMIZZATI LINCIDENZACUMULATIVA AD UN FOLLOW-UP DI 9-12 MESI ERA: 0.7 – 1.2% Ma nei vari registri, più rappresentativi della pratica clinica quotidiana, vengono riportate incidenza 2-3 volte superiori Una differenza sostanziale rispetto agli stents metallici è il PATTERN TEMPORALE della trombosi che non infrequentemente viene osservata oltre i 12 mesi dalla procedura (vey late) Kaul S et al; JACC 2007

27 Wenaweser MS et al, Am Heart J 2008: DES THROMBOSIS (follow-up 4 years) Wenaweser P et al; JACC 2008: ,4-0,6% year

28 Chechi T et al; JACC 2008: month OUTCOMES Ninety-two (80%) of these STs presented as STEMI 20.9% vs 10.2% 31.4% vs 17.3% MACCE: major adverse cardiovascular and cerebrovascular events

29 Riperfusione efficace Chechi T et al; JACC 2008: STEMI with STSTEMI without ST

30 INDICAZIONI ALLUSO DEI DES

31 PCI 2005 Classe I In patients who have undergone PCI, clopidogrel 75 mg daily should be given for at least 3 months after sirolimus stent implantation, and 6 months after paclitaxel stent implantation, and ideally up to 12 months in patients who are not at high risk of bleeding. (Level of Evidence: B) PCI UPDATE 2007 Classe I For all post-PCI stented patients receiving a DES, clopidogrel 75 mg daily should be given for at least 12 months if patients are not at high risk of bleeding. (Level of Evidence: B)

32 For patients with clinical features associated with stent thrombosis, such as renal insufficiency, diabetes, or procedural characteristics such as left main, bifurcating left main, single patent coronary vessel, multiple stents or treatment of a bifurcation lesion, extended DAT beyond 1 year may be reasonable. PCI 2007 update Classe IIb Continuation of clopidogrel therapy beyond 1 year may be considered in patients undergoing DES placement (Level of Evidence: C)

33 DES THROMBOSIS OPEN ISSUES Se linterruzione della doppia antiaggregazione rappresenta il fattore predittivo indipendente di maggior peso per la trombosi dello stent, occorre ricordare che una percentuale variabile da un terzo alla metà dei casi avviene sotto doppia antiaggregazione (Holmes DR et al; JACC 2007)

34 Antiplatelets treatment Main open issues: Need of pretreatment Loading Dose Length and Dose of long term therapy Clopidogrel low responsiveness Perioperative Management in patients with stents Dual antiplatelet therapy and Chronic oral Anticoagulation

35 Variability in platelet responsiveness to 300 mg loading dose of clopidogrel among 544 individuals. Serebruany VL et al, JACC 2005;45:

36 Impact of Platelet Reactivity After Clopidogrel Administration on Drug-Eluting Stent Thrombosis Buonamici P et al, JACC 2007 Incidence ST: 8.6% NR vs 2.3% R, p=0,001

37 ISAR-CHOICE 2 A double-blind, randomized study on platelet aggregation in pts treated with a daily dose of 150 or 75mg of clopidogrel for 30 days. 60 stable pts, < 12 h from PCI pretreated with 600mg CLO Randomization 150mg for 30 d 75mg for 30 d Platelet function testing 5 µM ADP-aggregation (%) 65±12 45±20 P <0.001 Von Beckerath, E Heart J 2007; 28:

38 High Clopidogrel maintaining dosage improves long-term clinical outcomes in Pts with ACS undergoing DES implantation 634 ACS pts, PCI + DES pretreated with 600mg CLO Randomization 150mg for 30 d 75mg for 30 d Clinical evaluation (mean 18mo) Han Y, TCT mg for 12 mo All MI TVR death ns major bleed trasfusion P <0.001 ns

39 PCI – AHA 2005 Classe IIb For patients in whom subacute thrombosis may be catastrophic (unprotected left main, bifurcating left main, or single patent coronary vessel), it is reasonable to perform platelet aggregation studies, and if < 50% platelet inhibition, consider 150 mg/day (clopidogrel).

40 Novel platelet receptor antagonist Prasugrel AZD6140 Cangrelor ADP P2Y 12 BMS BS GR TERUTROBAN (S188886) TP (TXA2/PGH2) SCH E5555 PAR1 (Trombina)

41 Comparison with Higher Dose Clopidogrel P< for each IPA (%; 20 M ADP) Hours 14 Days IPA (%; 20 M ADP) P< Prasugrel 10 mg Clopidogrel 150 mg Wiviott et al Circ 2007 N=201 Prasugrel 60 mg Clopidogrel 600 mg

42 HR 0.81 ( ) P= Prasugrel Clopidogrel Days Endpoint (%) HR 1.32 ( ) P=0.03 Prasugrel Clopidogrel events 35 events Balance of Efficacy and Safety CV Death / MI / Stroke TIMI Major NonCABG Bleeds NNT = 46 NNH = 167 TRITON-TIMI 38 N Engl J Med 2007 RR – 24% RR + 32%

43 HR 0.81 ( ) P= Prasugrel Clopidogrel Days Endpoint (%) HR 1.32 ( ) P=0.03 Prasugrel Clopidogrel events 35 events Balance of Efficacy and Safety CV Death / MI / Stroke TIMI Major NonCABG Bleeds NNT = 46 NNH = 167 TRITON-TIMI 38 N Engl J Med 2007 RR – 24% RR + 32% NET CLINICAL BENEFIT favours PRASUGREL P 12,2% vs C 13,9% P = 0,004

44 Bleeding Risk Subgroups Therapeutic Considerations Significant Net Clinical Benefit with Prasugrel 80% MD 10 mg Reduced MD Guided by PK Age > 75 or Wt < 60 kg 16% Avoid Prasugrel Prior CVA/TIA 4%

45 TIMI Major NonCABG Bleeding Antman EM et al, JACC 2008

46 Antiplatelets treatment Main open issues: Need of pretreatment Loading Dose Length and Dose of long term therapy Clopidogrel low responsiveness Perioperative Management in patients with stents Dual antiplatelet therapy and Chronic oral Anticoagulation

47 ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery

48 Surgery Room 5 day before Stop clopidogrel 2 day after Restart clopidogrel 0 ASA 80 mg/d ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery Holmes DR et al; JACC 2007 Class IIa Class IIa; level of evidence: C

49 Surgery Room 5 day before Stop clopidogrel 1 day after Restart clopidogrel 0 Interventi chirurgici a maggior rischio di sanguinamento LMWH 7 day before start STOP GISE day before Stop ASA Restart ASA 3 day after

50 Surgery Room 3 day before Stop clopidogrel 1 day after Restart clopidogrel 0 ASA 80 mg/d Interventi chirurgici a basso rischio di sanguinamento LMWH 7 day before start STOP GISE 2008

51 ACCP 2008 continuing In patients with a bare metal coronary stent (BMS) who require surgery within 6 weeks of stent placement, we recommend continuing aspirin and clopidogrel in the perioperative period (Grade 1C). continuing In patients with a drug-eluting coronary stent (DES) who require surgery within 12 months of stent placement, we recommend continuing aspirin and clopidogrel in the perioperative period (Grade 1C). against In patients with a coronary stent who have interruption of antiplatelet therapy before surgery, we suggest against the routine use of bridging therapy with UFH, LMWH, direct thrombin inhibitors, or glycoprotein IIb/IIIa inhibitors (Grade 2C).

52 Antiplatelets treatment Main open issues: Need of pretreatment Loading Dose Length and Dose of long term therapy Clopidogrel low responsiveness Perioperative Management in patients with stents Dual antiplatelet therapy and Chronic oral Anticoagulation

53 ASAASA + TiclopidinaASA + Warfarin Stent thrombosis STARS 2,9%0,5%2,7% ISAR -0,8%5,4%

54 Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding A A + W A + W + C A = ASA; W = WARFARIN; C = CLOPIDOGREL Khurram Z et al J Invasive Cardiol 2006

55 TROMBOSI DELLO STENT DES ed anticoagulazione (LG FA 2006)

56 STENTS e WARFARIN 1)AD ELEVATO RISCHIO EMBOLICO + BMS ACCP 2008 (Grado 2 C) Clopidogrel + ASA + warfarin per 4 settimane Warfarin + ASA successivamente (con INR target 2-2,5) 2) A RISCHIO EMBOLICO BASSO o MODERATO + BMS (+ DES) ASA + Clopidogrel per 4 settimane (1 anno se DES)ASA + Clopidogrel per 4 settimane (1 anno se DES) ASA successivamenteASA successivamente 3) 3) ELEVATO RISCHIO EMBOLICO + DES ACCP 2008 (Grado 2C) ASA + CLOPIDOGREL + WARFARIN (9-12 mesi)ASA + CLOPIDOGREL + WARFARIN (9-12 mesi)

57 TROMBOSI DELLO STENT DES ed anticoagulazione (LG FA 2006) 1.Gli autori ritengono che il clopidogrel sia il farmaco più importante per il mantenimento della pervietà dello stent. mantenimento della pervietà dello stent. 2. laggiunta di aspirina alla terapia anticoagulante comporta più rischi che benefici. 3. La terapia di mantenimento dovrebbe consistere nellassociazione tra clopidogrel (75 mg/die) + warfarin (con INR tra 2 e 3) per 9-12 mesi clopidogrel (75 mg/die) + warfarin (con INR tra 2 e 3) per 9-12 mesi 4. Dopo 9-12 mesi, sospensione del clopidogrel e proseguimento del warfarin come monoterapia come monoterapia CLASSE IIb; livelllo di evidenza: C

58

59

60 VI RINGRAZIO PER LA BONTA PER LA BONTA

61 PCI – AHA 2007 update (ASA) Classe I Patients already taking daily long-term aspirin therapy should take 75 mg to 325 mg of aspirin before PCI is performed. Patients already taking daily long-term aspirin therapy should take 75 mg to 325 mg of aspirin before PCI is performed. (Level of Evidence: A). Patients not already taking daily longterm aspirin therapy should be given 300 mg to 325 mg of aspirin at least 2 hours and preferably 24 hours before PCI is performed. Patients not already taking daily longterm aspirin therapy should be given 300 mg to 325 mg of aspirin at least 2 hours and preferably 24 hours before PCI is performed. (Level of Evidence: C)

62 PCI – AHA 2007 update Classe IIa For patients with an absolute contraindication to aspirin, it is reasonable to give a 300-mg to 600-mg loading dose of clopidogrel, administered at least 6 hours before PCI, and/or GP IIb/IIIa antagonists, administered at the time of PCI. For patients with an absolute contraindication to aspirin, it is reasonable to give a 300-mg to 600-mg loading dose of clopidogrel, administered at least 6 hours before PCI, and/or GP IIb/IIIa antagonists, administered at the time of PCI. (Level of Evidence: C)

63 ACCP 2008 For patients undergoing PCI with a DES, we recommend aspirin (75–100 mg/d) plus clopidogrel (75 mg/d for at least 12 months) [Grade 1A for 3 to 4 months; Grade 1B for 4 to 12 months].

64 PCI – AHA 2007 update (ASA) Classe I (Level of Evidence: B). After PCI, in patients without allergy or increased risk of bleeding, aspirin 162 mg to 325 mg daily should be given for at least: 1 month after BMS implantation, 1 month after BMS implantation, 3 months after sirolimus-eluting stent implantation, and 3 months after sirolimus-eluting stent implantation, and 6 months after paclitaxel-eluting stent implantation, 6 months after paclitaxel-eluting stent implantation, after which daily long-term aspirin use should be continued indefinitely at a dose of 75 mg to 162 mg. after which daily long-term aspirin use should be continued indefinitely at a dose of 75 mg to 162 mg. Classe IIa In patients for whom the physician is concerned about risk of bleeding, a lower dose of 75 mg to 162 mg of aspirin is reasonable during the initial period after stent implantation. In patients for whom the physician is concerned about risk of bleeding, a lower dose of 75 mg to 162 mg of aspirin is reasonable during the initial period after stent implantation. (Level of Evidence: C)

65 Ticlopidina Azione ritardata (fino a 3 giorni) Duplice somministrazione giornaliera Effetti collaterali (10.6% CLASSICS): a) Rush cutanei, disturbi gastrointestinali b)Depressione midollare con trombocitopenia e neutropenia (2%) nei primi 3 mesi (controllo emocromo ogni 2 settimane) c)Porpora trombotica trombocitopenica (raro)

66 Clopidogrel CLASSICS (2000): Ticlopidina e clopidogrel hanno efficacia antitrombotica simile 1)Clopidogrel con più bassa frequenza di effetti collaterali (5.3% vs. 10.6% ticlopidina)

67 Clopidogrel - vantaggi Rapido ed elevato livello di antiaggregazione dopo carico orale Bassa incidenza di depressione midollare Bassa incidenza di effetti collaterali cutanei e gastrointestinali Monosomministrazione giornaliera

68

69

70

71


Scaricare ppt "LA TERAPIA ANTIAGGREGANTE PRIMA E DOPO STENT Francesco Bellandi U.O. Cardiologia - Ospedale di Prato IL DIVENIRE CLINICO IN CARDIOLOGIA Firenze 31 Ottobre."

Presentazioni simili


Annunci Google