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1 Speaker s name: Thomas Cuisset, MD, PhD X I have the following poten>al conflicts of interest to report: x Consul*ng: Astra Zeneca, Daiichi Sankyo, Eli Lilly, Medicines Company Employment in industry Stockholder of a healthcare company Owner of a healthcare company x Others: Lecture Fee AbboF Vascular, Astra Zeneca, Biotronik, Boston Scien*fic, Cordis, Daichi Sankyo, Edwards, Eli Lilly, Hexacath, Iroko Cardio, Medtronic, Servier, Terumo I do not have any poten>al conflict of interest

2 Cas Clinique: SCA ST+ Thomas Cuisset, CHU Timone, Marseille COPACAMU, Marseille 2015

3 Contexte pré Hospitalier 6 am: Coup de fil du SAMU «J ai un homme de 64 ans avec un antérieur à la 2 ème heure» Traitement préhospitalier?

4 Traitement pré hospitalier Aspirine 250 mg An*coagula*on: HNF 4000 IU P2Y12 blockers?

5 Ticagrelor dans le STEMI: étude PLATO Death, MI, stroke 10.8 % 9.4 % Pas d excès d hémorragie dans STEMI Steg et al, Circula*on 2010

6 Prasugrel dans le STEMI: étude TRITON Propor*on of pa*ents (%) Death, MI, stroke Clopidogrel Prasugrel HR=0.79 ( ) p=0.02 RRR=21% Clopidogrel Prasugrel Time (Days) Pas d excès d hémorragie dans STEMI N=3534 Montalescot et al. Lancet 2009

7 Mortalité dans STEMI avec nouveaux AAP HR=0.76, p=0.11 HR=0.82, p= % 4.3% Prasugrel Clopidogrel 4 2 5% 6.1% Ticagrelor Clopidogrel 0 Death 0 Death TRITON STEMI, n=3534 Montalescot et al, Lancet 2009 PLATO STEMI, n=7544 Steg et al, Circula*on 2010

8 Bloqueurs P2Y12 dans le STEMI Nouveaux AAP comme gold standard dans STEMI mais encore clopidogrel chez 1/3 pa*ents (âgés, risque hémorragique, an*coagula*on)

9 Timing des nouveaux bloqueurs P2Y12 dans STEMI? Pré- hospitalier vs. Cathlab?

10 Study popula>on and design STE- ACS planned for PCI (N = 1862) Randomised, double- blind Ticagrelor 180 mg loading dose Pre- hospital Placebo loading dose Placebo loading dose In- Hospital Ticagrelor 180 mg loading dose 70% ST- segment eleva>on resolu>on pre- PCI Primary Objec>ves OR TIMI flow grade 3 of MI culprit vessel at ini>al angiography Ticagrelor 90 mg/bid 30 days Montalescot G et al. Am Heart J. 2013

11 Baseline pa>ent characteris>cs Ticagrelor pre- hospital (n=909) Ticagrelor in- hospital (n=953) Age, years; mean ± SD 60.6 ± ± years; % Female, % Weight, kg; mean ± SD 80.4 ± ± 15.6 BMI 30 kg/m 2, % Diabetes mellitus, % TIMI risk score group, % > Killip class I, % BMI, body mass index; SD, standard devia*on

12 Median >mes to pre- and in- hospital steps Onset of Symptoms Randomiza>on EKG Pre- hospital LD1 LD2 EKG Pre- PCI Angiography PCI

13 Co- primary efficacy endpoints (mitt) Absence of ST- segment eleva>on 70% Primary objec>ve p=ns Pre- hospital In- hospital p=0.055 (NS) Pre- PCI Pre- hospital n=774 In- hospital n=824 Post- PCI Pre- hospital n=713 In- hospital n=743 Pre- PCI Post- PCI 1 hour aier PCI

14 Major adverse CV events up to 30 days: Kaplan Meier curves Event rate (KM %) Ticagrelor pre- hospital Ticagrelor in- hospital Ticagrelor pre- hospital 41/906 (4.5%) versus *cagrelor in- hospital 42/952 (4.4%) OR 1.03 (95% CI 0.66, 1.0); p= Time (days) Major adverse CV events: death, myocardial infarc*on, stroke or urgent revascularisa*on

Definite stent thrombosis up to 30 days P=0.0225 Ticagrelor pre- hospital 2/906 (0.

15 Definite stent thrombosis up to 30 days P= Ticagrelor pre- hospital 2/906 (0.2%) versus Ticagrelor in- hospital 11/952 (1.2%) OR 0.19 (95% CI 0.04, 0.86), P= days

In- hospital *cagrelor Ticagrelor pre- hospital 2/906 (0.

16 Ticagrelor and definite stent thrombosis PLATO In- hospital Ticagrelor vs. Clopidogrel ATLANTIC Pre- hospital Ticagrelor vs. In- hospital *cagrelor Ticagrelor pre- hospital 2/906 (0.2%) versus *cagrelor in- hospital 11/952 (1.2%) OR 0.19 (95% CI 0.04, 0.86), P= HR=0.67; 95% CI= ; p=0.009 Steg PG, et al. Circula*on 2013;128: Montalescot G, et al. ESC sept 1st 2014.

17 ATLANTIC: conclusion Pas le temps d agir avant l angioplas*e Critère primaire neutre Bénéfice en post ACT Résolu*on ST / thrombose stent

VASP- PRI according to groups (bars) 100 Primary objec>ve p=ns p=ns p=ns Pre Hospital (Pre- treatment) In Hospital (CathLab) 80 % VASP - PRI 60 40 p=ns p=ns 20 0

18 VASP- PRI according to groups (bars) 100 Primary objec>ve p=ns p=ns p=ns Pre Hospital (Pre- treatment) In Hospital (CathLab) 80 % VASP - PRI p=ns p=ns 20 0 T1 (PrePCI) 41 T2 (End of PCI) 1h17 T3 (H1 Post PCI) 3h02 T4 (H6 PostPCI) 7h21 T5 (Before MD) 13h23 LD1 LD2 Pre- PCI TIMI Flow and ST resolu>on Post- PCI ST resolu>on

19 Et la Safety?

20 Non- CABG- related bleeding events (PLATO defini>ons) - Safety popula>on

= NS p = NS p = NS p = NS p = NS p = NS TIMI STEEPLE pa*ents

21 Non- CABG- related bleeding events (TIMI, STEEPLE, GUSTO and ISTH defini*ons) - Safety popula*on pa*ents (%) pa*ents (%) p = NS p = NS p = NS p = NS p = NS p = NS TIMI STEEPLE pa*ents (%) pa*ents (%) p = NS p = NS p = NS p = NS p = NS p = NS GUSTO ISTH

22 Notre pra>que dans le STEMI STEMI «Pré traitement»: Aspirine + Nouveaux bloqueurs P2Y12 si pas de CI Ini>a>on du traitement en préhospitalier Pas d An>GPIIbIIIa en pré hospitalier

23 Pré traitement avant Coro par bloqueurs P2Y12 90% 60% 30% 0 0 Nouveaux bloqueurs P2Y12 Stable CAD / UA NSTEMI STEMI

24 Diagnos*c STEMI «facile» «J ai un homme de 64 ans avec un antérieur à la 2 ème heure»

25 Angioplas*e «certaine»

26 Charge thrombo*que «évidente»

27 Traitement pré hospitalier par bloqueurs P2Y12 NSTEMI - Incer*tude diagnos*que - Charge thrombo*que incertaine - Probabilité ICP 60% STEMI - Diagnos*c évident - Thrombus Probabilité ICP > 95% Pas de pré traitement «Pré traitement» Nouveaux AAP si pas CI

28 Traitement pré hospitalier Aspirine 250 mg An*coagula*on: HNF 4000 IU Ticagrelor 180 mg LD

29 Coronarographie

30 Stratégie Technique: TA suivi par ICP avec DES Medica*ons Inhibi*on plaquefaire > 2h avec nouvelles molécules Admission 40 min après AAP Drogue IV?

31 GPIIbIIIa OUI parce que: - Evidence scien*fique - IDM antérieur - Bas risque hémorragique / Radial

32 ICP IVA Après Thromboaspira*on Stent ac*f

33 Flux TIMI 3 Résolu*on ST

34 Merci

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