SCA: QUÉ ANTIAGREGANTE UTILIZAR? DAVID VIVAS, MD, PhD

Transcripción

1 SCA: QUÉ ANTIAGREGANTE UTILIZAR? DAVID VIVAS, MD, PhD

2 CONFLICTOS INTERÉS

3 ESQUEMA Introducción Clopidogrel, prasugrel y ticagrelor Ventajas y limitaciones Subgrupos de riesgo Complicaciones trombóticas: Trombosis Stent Complicaciones hemorrágicas: ACO Cirugía Implementación protocolos en nuestro medio

4 INTRODUCCIÓN SITUACIÓN ACTUAL DE LA ATEROTROMBOSIS Sociedad Española Cardiología, 2012

5 LA PLAQUETA Topol EJ, Yadav JS. Circulation 2000 Wallentin L. Eur Heart J 2009

6 á Inflamacion Coagulacion ADP ATP 5HT2A Gp Ib/V/ IX ADP, ATP, Ca 2+ Gp Ia/IIa Gp VI P2Y 12 CLOPIDOGREL G i P2Y 1 AC G q Epinefrina F. Coag Med. Inflam VASP AMPc VASP-P Ca 2+ flux P2X 1 ACTIVACION AMPc Trombina Gp IIb/ IIIa TXA 2 PAR 4 Fibrinógeno TPαR TPβR COX-1 AA PAR 1 AAS Trombina Gp IIb/ IIIa TXA 2 Vivas D, et al. Am J Cardiovasc Drugs 2010;10:217-23

7 CLOPIDOGREL Cummulative hazard rate Placebo * (n = 6,303) CURE TRIAL Clopidogrel * (n = 6,259) 20% Relative risk reduction p = Months of follow-up *On top of standard therapy (including ASA) The CURE Trial Investigators. N Engl J Med 2001; 345:

8 CLOPIDOGREL - VARIABILITY - reduced responsiveness to clopidogrel - Acute phase of treatment Long-term phase of treatment DM No-DM 80 P=0.001 P=0.04 8% 14% 38% 56% 78% 6% 24 hrs post 300 mg LD Non-responders (Platelet inhibition <10%) Platelet aggregation (%) P< Low responders (Platelet inhibition 10-29%) Responders (Platelet inhibition >30%) 0 T2DM No-DM T2DM No-DM ADP 20 µmol/l ADP 6 µmol/l Angiolillo DJ, Fernández-Ortiz A, et al. Diabetes. 2005;54: Angiolillo DJ, Fernández-Ortiz A, et al. J Am Coll Cardiol 2006;

9 á Inflamacion Coagulacion ADP ATP 5HT2A Gp Ib/V/ IX ADP, ATP, Ca 2+ Gp Ia/IIa Gp VI P2Y 12 PRASUGREL G i P2Y TICAGRELOR 1 AC G q Epinefrina F. Coag Med. Inflam VASP AMPc VASP-P Ca 2+ flux P2X 1 ACTIVACION AMPc Trombina Gp IIb/ IIIa TXA 2 PAR 4 Fibrinógeno PAR 1 TPαR TPβR COX-1 AA Trombina Gp IIb/ IIIa TXA 2 Vivas D, et al. Am J Cardiovasc Drugs 2010;10:217-23

10 Death, Myocardial Infarction, Stroke TRITON-TIMI 38 versus PLATO Incidence'of'1 'endpoint'(%)' 15' P"<"0.001"' P"<"0.001"' ' ' 12.1' 10' 11.7' 9.9' 9.8' Clopidogrel' Prasugrel' Ticagrelor' 5' 0' TRITON' PLATO' WivioH'SD'et'al.,'N"Engl"J"Med'2007;'WallenMn'L'et'al.,'N"Engl"J"Med'2009'

11 Safety'endpoint:'Major'bleeding' TRITON9TIMI'38'versus'PLATO' Proportion of population (%) Prasugrel Clopidogrel Days Wiviott SD et al., N Engl J Med 2007 Ticagrelor Clopidogrel 11.6% HR % ( ) 2.4% 1.8% HR 1.32 ( ) Wallentin L et al., N Engl J Med 2009

12 TIMI Major Bleeding TRITON-TIMI 38 versus PLATO Rate'of'non'CABG'bleeds'(%)' 3' P"="0.03"' P"="0.03"' ' Clopidogrel' ' 2.8' Prasugrel' 2.4' 2' 2.2' Ticagrelor' 1.8' 1' 0' TRITON' PLATO' WivioH'SD'et'al.,'N"Engl"J"Med'2007;'WallenMn'L'et'al.,'N"Engl"J"Med'2009'

13 Net Clinical Benefit Bleeding Risk Subgroups Prior Stroke / TIA Yes No Post-hoc analysis P int = Risk (%) Age >=75 < 75 P int = Wgt < 60 kg +3 >=60 kg P int = OVERALL Prasugrel Better HR Clopidogrel Better Wiviott SD et al NEJM 2007

14 Wallentin L et al NEJM 2009

15 Study'PopulaMon''' TRITONTTIMI'38'versus'PLATO' TRITONTTIMI'38:'prasugrel' STTelevaMon'myocardial'infarcMon'or'' hightrisk'non'sttelevamon'acute'coronary'syndromes'' ''''and' planned'pci,'proven'eligibility'for'pci' ' PLATO:'Mcagrelor'' STTelevaMon'myocardial'infarcMon'or' hightrisk'non'sttelevamon'acute'coronary'syndromes' ''''''' any'treatment'strategy' WivioH'SD'et'al.,'N"Engl"J"Med'2007;'WallenMn'L'et'al.,'N"Engl"J"Med'2009'

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17 TRITON TIMI-38: Stent End Point (%) Thrombosis ARC Definite + Probable Any Stent at Index PCI n=12,844 Clopidogrel 2.4 (142) 74 events Prasugrel 1.1 (68) HR 0.48 P< NNT= Days ARC = Academic Research Consortium; PCI = percutaneous coronary intervention Wiviott SD et al. N Engl J Med. 2007;357:

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25 RIESGO HEMORRÁGICO

26 High risk of ischemic events Sweet spot High risk of bleeding events Inhibition of platelet aggregation Ischemic risk Bleeding risk Ferreiro JL et al. Thromb Haemost 2010;103:

27 Dewilde WJM et al. Lancet 2013;381:

28 Dewilde WJM et al. Lancet 2013;381:

29 Dewilde WJM et al. Lancet 2013;381:

30 RIESGO HEMORRÁGICO USO ACO + CLOPIDOGREL SOLO! SEGURO

31 CIRUGÍA PRASUGREL! 7 DÍAS TICAGRELOR! 5 DÍAS (7 FICHA TÉCNICA!) Korte W et al. Thromb Haemost 2011;105:743-9

32 CIRUGÍA Pacientes tras implante de stent: Cirugía electiva: esperar hasta fin DAPT Cirugía semielectiva: individualizar Cirugía urgente: operar Considerar mantener AAS salvo alto riesgo sangrado De suspender inhibidor P2Y12: Clopidogrel (5-7d), prasugrel (7d), ticagrelor (5) Terapia puente?

33 PERFIL CLÍNICO IDEAL

34 INH. ADP P2Y12: RESUMEN Vivas D, et al. Rev Esp Cardiol. 2013

35 PROTOCOLO STEMI STEMI DM Bradiarritmia Artritis gotosa Disnea INHIBIDOR ADP P2Y12 Riesgo sangrado Anticoagulación Fibrinolisis Sit. económica Ictus Edad > 75 años Peso < 60kg Pre-Tto Clopi

36 PROTOCOLO STEMI STEMI DM Bradiarritmia PRASUGREL Artritis gotosa Disnea INHIBIDOR ADP P2Y12 Riesgo sangrado CLOPIDOGREL Anticoagulación Fibrinolisis Sit. económica Ictus Edad > 75 años TICAGRELOR Peso < 60kg Pre-Tto Clopi

37 PROTOCOLO NSTEMI NSTEMI ACTP No Pre-Tto PRASUGREL INHIBIDOR ADP P2Y12 Riesgo sangrado CLOPIDOGREL Anticoagulación Sit. económica Todo espectro Pre-Tto Clopi TICAGRELOR

38 MUCHAS GRACIAS