Nuevos antiagregantes plaquetarios

Transcription

1 XII Curso de Formación Continuada Nuevos antiagregantes plaquetarios marzo 214 Hotel El Montanyà. Seva, Barcelona

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

3 Concepto de pretratamiento en SCA SCACEST AAS SCASEST P2Y12 antg.? ICP1ª ICP Tto. Cirugía médico

4 Clopidogrel pretreatment and early risk 3-day death, MI & urg. TVR (%) PCI-CURE p=.1 CREDO No pretreatment Pretreatment p=.5 3 mg + 75 mg for median of 1 days 3 mg <6 hrs 6 24 hrs

5 % Cel. positivas Clopidogrel: Cúal es la dosis óptima? Activación GPIIb/IIIa (ADP2 M) p<.1 p=.9 3 mg ( n=2) 6 mg ( n=2) p=.5 4 p=.1 (MANOVA) 2 Basal 4h 24h 48h PostACTP Angiolillo DJ, Fernandez-Ortiz A, Bernardo E et al. Eur Heart J 24;25(21):193-1

6 Randomization ARMYDA-5 PRELOAD: Study design 3 days 536 Patients with Stable angina or NSTE-ACS undergoing coronary angiography Clopidogrel 6 mg given 4-8 hrs before angio N= 267 Clopidogrel 6 mg at the time of PCI N= 269 Medical Rx N= 72 Angiography CABG N= 55 N= 49 PCI 6 mg Preload N= 24 PCI 6 mg in-lab N= 25 Primary end point: cardiac death, MI, TVR 1 st blood sample 2 nd, 3 rd, 4 th and 5 th blood samples Baseline CKa-MB Troponin-I PRU Di Sciascio G et al. J Am Coll Cardiol 21;56: At the time of PCI PRU 2 hrs after PCI PRU 8 and 24 hrs after PCI CK-MB Troponin-I PRU

7 Cumulative incidence of MACE (%) ARMYDA-5 PRELOAD: Primary endpoint Adverse events at 3 days (Clopidogrel in-lab load vs preload) In-lab load Preload p= Days after PCI Di Sciascio G et al. J Am Coll Cardiol 21;56:55-557

8 ARMYDA-5 PRELOAD: Safety secondary end point p= In-lab load Preload Major bleeding Minor bleeding Di Sciascio G et al. J Am Coll Cardiol 21;56:55-557

9 Inhibition of platelet aggregation (%) New P2Y12 Antagonists Early onset and high inhibition 1 Loading dose Pre-treatment with aspirin and a P2Y12 antagonist is * * * * a class I recommendation * and is common p<.1 practice vs. Clop 3 mg Pras 6 mg LD 8 or 6 mg LD* for the treatment of NSTE-ACS! p<.1 vs. Clop 3 mg * 6 Clop 6 mg LD In CURE, patients were managed conservatively! p<.5 vs. Clop 3 mg 4! In TRITON, patients were not Clop pretreated 3 mg LD before cath 2 In PLATO, patients were pretreated before cath mean ± SEM No trial had ever randomized patients 2 μm ADP presenting with NSTE-ACS, invasively managed, to pre- Time after loading dose (hrs) treatment with clopidogrel, prasugrel or ticagrelor vs. no pre-treatment LD, Loading dose ACCOAST 1. Wiviott SD et al. Am Heart J. 26;152: Payne CD et al. Am J Cardiol. 26;98:S8.

10 ACCOAST design NSTEMI + Troponin 1.5 times ULN local lab value Clopidogrel naive or on long term clopidogrel 75 mg Randomize 1:1 Double-blind n~41 (event driven) Prasugrel 3 mg Placebo CABG or Medical Management (no more prasugrel) Coronary Angiography Prasugrel 3 mg Coronary Angiography Prasugrel 6 mg CABG or Medical Management (no prasugrel) PCI PCI Prasugrel 1 mg or 5 mg (based on weight and age) for 3 days 1 Endpoint: CV Death, MI, Stroke, Urg Revasc, GP IIb/IIIa inh. Bailout, at 7 days Montalescot G et al. Am Heart J 211;161:65-656

11 Pharmacodynamic Sub-Study 35 3 Placebo LD1 6 mg LD2 Pre-treatment (3/3) No Pre-treatment (/6) *P<.5 P2Y 12 Reaction Units mg LD1 Approximate time of PCI * * 3 mg LD2 Pre LD1 (baseline) Pre LD Hours (post LD2) Data presented as median ± SEM. * p<.5 relative to the No pre-treatment group. LD = loading dose. Pretreatment=Prasugrel 3 mg/prasugrel 3 mg; No Pre-treatment=Placebo/Prasugrel 6 mg

12 Endpoint (%) 1 Efficacy End days (All Patients) 15 Pre-treatment 1. CV Death, MI, Stroke, UR, GPIIb/IIIa Bailout Pre-treatment No Pre-treatment 9.8 No Pre-treatment Hazard Ratio, 1.2 (95%.84, 1.25) P=.81 Hazard Ratio,.997 (95%.83, 1.2) P=.98 No. at Risk, Primary Efficacy End Point: No pre-treatment Pre-treatment Days From First Dose

13 Endpoint (%) All TIMI (CABG or non-cabg) Major Bleeding (All Treated patients) 5 4 Hazard Ratio, 1.9 (95% 1.19, 3.2) P=.6 Hazard Ratio, 1.97 (95% 1.26, 3.8) P=.2 3 Pre-treatment 2.6 Pre-treatment All TIMI Major Bleeding 1 No Pre-treatment 1.4 No Pre-treatment 1.5 No. at Risk, All TIMI Major Bleeding: No pre-treatment Pre-treatment Days From First Dose

14 All TIMI Major Bleeding for Prespecified Subgroups Through 7 days (All Treated Patients) Overall (pre-treatment vs. no pre-treatment) PCI CABG Medical Management* Age <75 years >75 years Sex Male Female Weight <6 kg* >6 kg Diabetes Yes No Time from Sx to LD <median >median Time from first LD to angio/pci <median >median CRUSADE score <median >median GRACE score <14 >14 Access Femoral Radial Region Eastern Europe/Israel Western Europe/Canada Total Patients 433 Pre-tx (%) 52 (2.55) Hazard Ratio (95% CI) 1.9 (1.19, 3.2) (1.57) 11 (.8) 1.98 (.96, 4.9) (2.66) 16 (13.68) 1.59 (.85, 2.98) (.97) (.) NE (2.16) 22 (1.33) 1.64 (.96, 2.78) (4.29) 5 (1.46) 2.95 (1.8, 8.5) (2.9) 21 (1.46) 1.43 (.82, 2.49) (3.8) 6 (1.8) 3.61 (1.46, 8.95) 25 5 (4.85) 1 (.98) NE (2.43) 26 (1.37) 1.78 (1.1, 2.87) 82 6 (1.45) 6 (1.47).98 (.32, 3.5) (2.83) 21 (1.32) 2.16 (1.29, 3.62) (2.75) 18 (1.86) 1.5 (.83, 2.71) (2.4) 9 (.89) 2.7 (1.25, 5.8) (2.72) 12 (1.2) 2.28 (1.16, 4.51) (2.35) 15 (1.53) 1.54 (.81, 2.93) (2.22) 18 (1.16) 1.92 (1.9, 3.41) (3.54) 8 (2.) 1.76 (.75, 4.12) No Pre-tx (%) 27 (1.35) (2.23) 1 (.98) 2.29 (1.9, 4.81) (2.97) 15 (1.71) 1.75 (.93, 3.28) (2.54) 18 (1.58) 1.62 (.9, 2.91) (2.53) 8 (.95) 2.67 (1.19, 6.) 14 (1.62) 5 (.6) 2.69 (.97, 7.47) 38 (3.24) 22 (1.89) 1.74 (1.3, 2.94) Interaction P-value Pre-treatment better No pre-treatment better *Hazard ratio not evaluated for <1 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.

15 Pretratamiento en SCASCEST: preguntas 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?