Nuevos antiagregantes plaquetarios XII Curso de Formación Continuada marzo 2014 Hotel El Montanyà. Seva, Barcelona

¿Sigue siendo importante el pretratamiento con los nuevos antiagregantes plaquetarios?

Concepto de pretratamiento en SCA SCACESTSCASEST ICP1ª ICP Tto.médico Cirugía AAS P2Y12 antg. ?

Clopidogrel pretreatment and early risk PCI-CURECREDO 30-day death, MI & urg. TVR (%) p=0.01p= mg + 75 mg for median of 10 days 300 mg <6 hrs6–24 hrs No pretreatment Pretreatment

Clopidogrel: ¿Cúal es la dosis óptima? Clopidogrel: ¿Cúal es la dosis óptima? p< p=0.009 p=0.005 p=0.001 (MANOVA) Basal4h24h48h PostACTP Activación GPIIb/IIIa (ADP2  M) % Cel. positivas Angiolillo DJ, Fernandez-Ortiz A, Bernardo E et al. Eur Heart J 2004;25(21): mg ( n=20) 600 mg ( n=20)

PCI 600 mg Preload N= 204 Primary end point: cardiac death, MI, TVR 536 Patients with Stable angina or NSTE-ACS undergoing coronary angiography 30 days Clopidogrel 600 mg given 4-8 hrs before angio N= 267 Clopidogrel 600 mg at the time of PCI N= 269 PCI 600 mg in-lab N= 205 Medical Rx N= 72 CABG N= 55 N= 409 CKa-MB Troponin-I PRU 1 st blood sample Baseline 2 nd, 3 rd, 4 th and 5 th blood samples At the time of PCI 2 hrs after PCI 8 and 24 hrs after PCI PRUCK-MB Troponin-I PRU ARMYDA-5 PRELOAD: Study design Randomization Angiography Di Sciascio G et al. J Am Coll Cardiol 2010;56:

In-lab load Preload p= Days after PCI Cumulative incidence of MACE (%) ARMYDA-5 PRELOAD: Primary endpoint Adverse events at 30 days (Clopidogrel in-lab load vs preload) Di Sciascio G et al. J Am Coll Cardiol 2010;56:

Major bleeding In-lab load Preload % of patients p=0.42 Minor bleeding 0 ARMYDA-5 PRELOAD: Safety secondary end point Di Sciascio G et al. J Am Coll Cardiol 2010;56:

1. Wiviott SD et al. Am Heart J. 2006;152: Payne CD et al. Am J Cardiol. 2006;98:S8. New P2Y12 Antagonists Early onset and high inhibition mean ± SEM 20 μM ADP Time after loading dose (hrs) Inhibition of platelet aggregation (%) Clop 300 mg LD Loading dose † p<0.001 vs. Clop 300 mg † † ! † ! p<0.05 vs. Clop 300 mg ! Clop 600 mg LD * * * * * * p<0.001 vs. Clop 300 mg or 600 mg LD* Pras 60 mg LD 0 LD, Loading dose Pre-treatment with aspirin and a P2Y12 antagonist is a class I recommendation and is common practice for the treatment of NSTE-ACS In CURE, patients were managed conservatively In TRITON, patients were not pretreated before cath In PLATO, patients were pretreated before cath No trial had ever randomized patients presenting with NSTE-ACS, invasively managed, to pre- treatment with clopidogrel, prasugrel or ticagrelor vs. no pre-treatment …… ACCOAST

ACCOAST design Prasugrel 30 mg Prasugrel 60 mg Prasugrel 30 mg Prasugrel 10 mg or 5 mg (based on weight and age) for 30 days PCI 1 ° Endpoint: CV Death, MI, Stroke, Urg Revasc, GP IIb/IIIa inh. Bailout, at 7 days Placebo Coronary Angiography n~4100 (event driven) Coronary Angiography PCI CABG or Medical Management (no prasugrel) CABG or Medical Management (no more prasugrel) Montalescot G et al. Am Heart J 2011;161: Randomize 1:1 Double-blind NSTEMI + Troponin ≥ 1.5 times ULN local lab value Clopidogrel naive or on long term clopidogrel 75 mg

Pharmacodynamic Sub-Study Data presented as median ± SEM. * p<0.05 relative to the No pre-treatment group. LD = loading dose. Pretreatment=Prasugrel 30 mg/Prasugrel 30 mg; No Pre-treatment=Placebo/Prasugrel 60 mg

Days From First Dose Endpoint (%) CV Death, MI, Stroke, UR, GPIIb/IIIa Bailout No. at Risk, Primary Efficacy End Point: No pre-treatment Pre-treatment Pre-treatment Hazard Ratio, (95% 0.83, 1.20) P=0.98 P=0.81 (95% 0.84, 1.25) Hazard Ratio, 1.02 No Pre-treatment No Pre-treatment 1° Efficacy End days (All Patients)

All TIMI (CABG or non-CABG) Major Bleeding (All Treated patients) Days From First Dose Endpoint (%) All TIMI Major Bleeding Pre-treatment 2.9 Pre-treatment 2.6 No Pre-treatment 1.5 No Pre-treatment No. at Risk, All TIMI Major Bleeding: No pre-treatment Pre-treatment Hazard Ratio, 1.97 (95% 1.26, 3.08) P=0.002 Hazard Ratio, 1.90 (95% 1.19, 3.02) P=0.006

*Hazard ratio not evaluated for <10 events. †Interaction p-value is from a Cox proportional hazards model with treatment, subgroup, and the treatment-by-subgroup interaction as fixed effects; ‡CRUSADE score is a post-hoc analysis; PCI includes 11 patients with PCI + CABG. All TIMI Major Bleeding for Prespecified Subgroups Through 7 days (All Treated Patients)

¿Existe evidencia del beneficio del pretatamiento con clopidogrel? ¿Necesitan todos los pacientes pretratamiento? Con los nuevos antiagregantes, ¿es importante el pretratamiento? ¿Es igual con prasugrel que con tricagrelor? ¿Influye la precocidad en realizar la coronariografía? ¿ Dónde iniciar el tratamiento de los nuevos antiagregantes?, ¿ambulancia?, ¿urgencias?, ¿lab. hemodinámica? Pretratamiento en SCASCEST: preguntas