Διαχείριση των Οξέων Στεφανιαίων Συνδρόμων: Ο ρόλος των αντιαιμοπεταλιακών και η βέλτιστη διάρκεια της διπλής αντιαιμοπεταλιακής αγωγής

Transcription

1 Διαχείριση των Οξέων Στεφανιαίων Συνδρόμων: Ο ρόλος των αντιαιμοπεταλιακών και η βέλτιστη διάρκεια της διπλής αντιαιμοπεταλιακής αγωγής Στάκος Δημήτριος Παν. Καρδιολογική Κλινική Αλεξανδρούπολη DAPT duration Thrombotic events Bleeding Risk

2 To disclaimer: «Presentations are intended for educational purposes only and do not replace independent professional judgment. Statements of fact and opinions expressed are those of the speakers individually and, unless expressly stated to the contrary, are not the opinion or position of AstraZeneca. AstraZeneca does not endorse or approve, and assumes no responsibility for, the content, accuracy or completeness of the information presented»

3 Δήλωση σύγκρουσης συμφερόντων (conflict of interest) Ο ομιλητής έχει λάβει οικονομική ενίσχυση με μορφή honoraria και Research Grants από ASTRAZENECA TERUMO DIAGNOSTICS BIOTRONIK Orbus Neich ELPEN

4 The role of platelets in atherothrombosis

5 Most PLTs never undergo firm adhesion to the endothelium collagen-- vwfactor PLTs PGI 2 NO camp and cgmp; CD39 ectoadpase, heparan sulfate, tissue plasminogen activator

6 This changes after plaque rupture or erosion.. Stakos DA, et al. Curr Vasc Pharmacol Sub-endothelial layers are exposed

7 or in uncovered stent struts

8 Platelet activation and adhesion begins

9 Rolling at high shear Collagen / vw / vitronectin/ laminin, fibronectin

10 Collagen / vw / vitronectin/ laminin, fibronectin

11 Collagen / vw / vitronectin/ laminin, fibronectin

12 Collagen / vw / vitronectin/ laminin, fibronectin

13 Collagen / vw / vitronectin/ laminin, fibronectin

14 Collagen / vw / vitronectin/ laminin, fibronectin

15 Collagen / vw / vitronectin/ laminin, fibronectin

16 Collagen / vw / vitronectin/ laminin, fibronectin

17 Collagen / vw / vitronectin/ laminin, fibronectin

18 GP Ib/V/IX Collagen / vw / vitronectin/ laminin, fibronectin

19 SECRETION OF PLATELET AGONISTS TXA 2 scd40l T vwf

20 ADP RECEPTORS P2Y12R AND P2Y1R P2Y 12 R Dense granule release from adjacent PLTs Gi camp Ca++ dense granule release alpha granule release (P-selectin expression) PLT recruitment GPIIb/IIIa inactive Pro-Coagulation TXA 2 generation Enhancement of TXA2/TH PLT activation

21 Stakos D, et al. Eur Heart J. 2015

22 Antiplatelets in acute coronary syndromes

23 Inhibition of platelet function and clinical outcomes (CVD prevention by ASPIRIN) Lancet, 2009

24 The P2Y 12 antagonists The combination of aspirin and clopidogrel was superior to aspirin alone in preventing vascular events in cardiac patients with unstable angina ASA + + ASA NEJM, 2001

25 or in those requiring percutaneous coronary intervention (PCI).. JAMA, 2002

26 Limitations of clopidogrel therapy Variable platelet-inhibition response Slow onset of action (Pro-drug) Irreversibly binds to platelet P2Y 12 receptors James S, et al. Am Heart J. 2009;157:

27 New antiplatelet agents

28 Ticagrelor: important characteristics Direct acting; does not require metabolic activation A rapid onset of inhibitory effect Greater and more consistent platelet inhibition than clopidogrel Less variability in individual response Reversibly binds to the P2Y 12 receptor Husted SE, et al. Eur Heart J. 2006;27: ; Cannon CP. J Am Coll Cardiol. 2007;50: ; Storey RF, et al. J Am Coll Cardiol. 2007;50: ; Gurbel PA, et al. Circulation. 2009;120:

29 PLATO study design ACS on aspirin randomized (N=18,624) Clopidogrel 300 mg / 75 mg Ticagrelor 180 mg / 90 mg x 2 12 mo Efficacy Endpoints: CVD, MI or stroke Total mortality, MI or stroke Death from any cause Safety Endpoints : Total major bleeding James S, et al. Am Heart J. 2009;157: ; Wallentin L, et al. N Engl J Med. 2009;361:

30 Cumulative incidence (%) PLATO: efficacy endpoint: (composite of CV death, MI or stroke) Clopidogrel Ticagrelor (HR, 0.84; 95% CI, ; P<0.001) Months after randomization Wallentin L, et al. N Engl J Med. 2009;361:

31 K-M estimated rate (% per year) PLATO: primary safety endpoint Ticagrelor Clopidogrel 11.6% 11.2% P=NS 5 (HR 1.04; 95% CI, ; P=0.43) Days from first IP dose

32 PLATO primary efficacy endpoint and incidence of stent thrombosis: Patients with intent for invasive treatment* Ticagrelor (n=6732) Clopidogrel (n=6676) HR for ticagrelor (95% CI) P value Stent thrombosis, n (%) Definite 71 (1.3) 106 (1.9) 0.67 ( ) Probable + Definite 118 (2.1) 158 (2.8) 0.75 ( ) Possible + Probable + Definite 155 (2.8) 202 (3.6) 0.77 ( ) *Intent for invasive or medical management declared prior to randomization. Wallentin L, et al. N Engl J Med. 2009;361:

33 Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes TRITON TIMI 38

34

35

36 Effectiveness vs Bleeding Risk in Antiplatelet Regiments ASA ASA +Clop ASA + Ticag ASA + Prasug Effectiveness Bleeding Risk Net Benefit When increased protection is needed?

37 High risk stents

38 55y F/ Unstable Angina / SLE

39 55y F/ Unstable Angina / SLE

40

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42 71y F/ Inferior MI / Prior Lysis Low risk stents..

43 Low risk stents..

44 Low risk stents..in High risk patients Stenotic Non-stenotic (Generally outnumber stenotic plaques) Libby P, Theroux P. Circulation 2005;111: ; Wentzel JJ et al. Cardiovasc Res 2012;96(2):

45 Initial Culprit Lesion vs New Atherosclerotic Plaque Recurrent Events Culprit lesion-related events 12.9% Non-culprit lesion-related events 11.6% Indeterminate events 2.7% ACS, acute coronary syndrome; MACE, major adverse cardiac events; PCI, percutaneous coronary intervention; PROSPECT, Providing Regional Observations to Study Predictors of Events in the Coronary Tree. Stone GW et al. N Engl J Med 2011;364:

46 Οξύ στεφανιαίο σύνδρομο ΣΤΕΦΑΝΙΟΓΡΑΦΙΑ Πολλαπλές πλάκες Υπολειπόμενη αντιδραστικότητα αιμοπεταλίων Αγγειακή φλεγμονή

47 ~1 in 5 patients post-mi, will suffer an MI, stroke or death within 3 years APOLLO 4-country analysis : Adjusted Incidence*

48 67y F, inf MI / prior Lysis / 2010

49 67y F, inf MI / prior Lysis / 2010

50 67 70y F, Unstable angina/ 2013

51 67 70y F, Unstable angina/ 2013

52 67 70y 72y F, Unstable angina/ 2015

53 67 70y 72y F, Unstable angina/ 2015

54

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56 ACS (patient reaction overtime..) Plaque reaction Platelet reaction Vessel reaction Extended antiplatelet protection..?

57 Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents ST 65% CLOP 35%PRASSUG MACE N Engl J Med 2014

58

59 Long term high risk patients Ticagrelor in long term use April no intervention 65y F, Inf MI

60 April 2017 July 2017, UA

61 April 2017 July 2017, UA

62 Potent antiplatelet drugs (accelerated nature of atherosclerosis)

63 47 y Male/ inf MI / shock

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65

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67 High Risk Stents in High Risk Patient

68 High Risk Stents in High Risk Patient

69 PEGASUS-TIMI 54: Inclusion Criteria Age 50 years old History of MI + high risk Bonaca MP et al. Am Heart J 2014;167: Bonaca MP et al. N Engl J Med 2015;372:

70 PEGASUS-TIMI 54: Major Exclusion Criteria Μη ανοχή του φαρμάκου (παρενέργειες) Bleeding disorder, history of ischaemic stroke or intracranial bleeding, central nervous system tumour or intracranial vascular abnormality Gastrointestinal bleeding within the previous 6 months or major surgery within the previous 30 days High risk of bradycardic events Severe hepatic or renal disease Bonaca MP et al. Am Heart J 2014;167: Bonaca MP et al. N Engl J Med 2015;372:

71

72 High risk stents in Low risk patients (Location) Low risk stents in High risk patients (Recurrent events) High risk stents in High risk patients (Location & events) Long term use

73 48 y BMI>50 Osteomyelitis / DVT Right Foot IVC filter On Anticoagulants Unstable Angina

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76 High risk stent (Location) long term use in high Bleeding Risk patient

77 PEGASUS-TIMI 54: Major Exclusion Criteria Planned use of anticoagulant therapy during the study period Bleeding disorder, history of ischaemic stroke or intracranial bleeding, central nervous system tumour or intracranial vascular abnormality Gastrointestinal bleeding within the previous 6 months or major surgery within the previous 30 days High risk of bradycardic events Severe hepatic or renal disease Bonaca MP et al. Am Heart J 2014;167: Bonaca MP et al. N Engl J Med 2015;372:

78 Θνητότητα μετά από θρόμβωση του stent ASA Clopidogrel Rivaroxaban 3m Clopidogrel Rivaroxaban 6m? Rivaroxaban

79 Conclusions ACS Patient Risk Assessment (accelerated atherosclerosis) Stent Risk Assessment (localization) Thrombotic Risk Assessment (Recurrent events) Bleeding Risk Assessment (mainly use of anticoagulants) Potency of antiplatelet agent Duration of antiplatelet agent