1

Recent advances in anti platelet therapy in ACS

Damien Coisne

WWW:cœur.plus.fr

2

ClarityCureAcuityOasis 5Early ACSAboardOn TimeTritonPlato

ExtractCaressFinesseEurotransfer

Oasis 6Oasis 5Horizon

Oasis 6Oasis 5Horizon

3

Overview

• New paradigm: Bleeding and coronary efficacy• Lesson from recent clinical trials (acuity, oasis)

• Main issues in anti platelets treatement for ACS• Early ACS, ABoard , • New antiplatelets agents :

– Triton, Plato, Acapulco, Current, Brave.

4

Coronary efficacy Bleeding

Net clinical result

5

6

7

Major predictors (NSTEMI)

Variable OR ajusté p

Age (aug/10 years) 1,22 0,0002

Female 1,36 0,0116

Renal failure antecedents 1,53 0,0062

Bleeding antecedents 2,18 0,014

GPIIb/IIIa use 1,86 < 0,0001

GRACE Registry : 24 045 patients with ACS (29 % angioplasty)

Predictive factors

7Moscucci M, et al. Predictors of major bleeding in acute coronary syndromes: the Glogal Registry of Acute Coronary Events (GRACE). Eur Heart J 2003 ; 24 : 1815-23.

8

Intra Hosp mortality related to major bleeding

Impact on mortality ?

8Moscucci M, et al. Predictors of major bleeding in acute coronary syndromes: the Glogal Registry of Acute Coronary Events (GRACE). Eur Heart J 2003 ; 24 : 1815-23.

9

Overview

• New paradigm: Bleeding and coronary efficacy• Lesson from recent clinical trials (acuity, oasis)

• Main issues in anti platelets treatement for ACS• Early ACS, ABoard , • New antiplatelets agents.

– Triton, Plato, Acapulco, Brave, Current

10

Prise en charge du STEMI

• Reperfusion en urgence- Angioplastie primaire avec/sans thrombo-aspiration- Thrombolyse/angioplastie de sauvetage- Angioplastie après thrombolyse réussie (3-24 heures)

• Traitement antithrombotique- Aspirine + clopidogrel- Anti-GPIIb/IIIa (si angioplastie)- Anticoagulant

ESC Guidelines for the Management of STE-ACS

Van de Werf.F, et al. The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology. European Heart Journal 2008 ; 29:2909-45.

10

11 ESC 2008

12

Prise en charge des AI/NSTEMI

• Stratification du risque

• Traitement anti-ischémique : β-bloquant, dérivés nitrés et antagonistes calciques

• Traitement antiagrégant plaquettaire adapté selon le risque initial

- Aspirine + clopidogrel chez tous les patients dans la mesure où il n’y a pas de contre-indication

- Anti-GPIIb/IIIa pour les patients à risque intermédiaire ou à haut risque

• Traitement anticoagulant recommandé chez tous les patients en association au traitement antiagrégant plaquettaire

• Revascularisation pour les patients à risque intermédiaire ou à haut risque (délai d’intervention selon sévérité initiale)

ESC Guidelines for the Management of NSTE-ACS

12

Le niveau de preuve est variable selon les différents traitements

Bassand JP, et al. The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology. European Heart Journal 2007, 28:1598-1660

13

14

Antiplatelets Strategy in ACS What’s new

Quel est l’impact de fortes doses de P2Y12 (Clopidogrel) sur la stratégie et les traitements adjuvants dans le cadre des SCA

STEMI (PPPCI), STEMI(Lysis), NSTEMI

Quid des nouvelles molécules?

15

NSTEMI

Leçons de 2 échecs relatifsEarly ACS et Aboard

Leçons de 2 échecs relatifsEarly ACS et Aboard

16

Study Design

High-risk NSTE ACS

n = 10,500

Primary Endpoint: 96-hr Death, MI, Recurrent ischemia requiring urgent revascularization, or Thrombotic bailout

Key Secondary Endpoint: 30-d Death or MI

Placebo / delayed provisional eptifibatide pre-PCI

Routine, early eptifibatide (180/2/180)

Randomize within 12 hours of presentation

Invasive strategy: 12 to 96 hours after randomization

2 of 3 high-risk criteria:1. Age > 60 years2. + CKMB or TnT/I3. ST or transient ST (Or age 50-59, h/o CVDand + CKMB or TnT/I)

Double bolus

17

Kaplan-Meier Curves for Primary EndpointD

eath

, M

I, R

IUR

or

TB

O (

%)

0

5

10

15

Time Since Randomization (Hours)

10.0%

9.3%

P = 0.23(stratified for intended early

clopidogrel use)

Delayed provisional eptifibatide

Routine early eptifibatide

0 8 16 24 32 40 48 56 64 72 80 88 96

RIUR, recurrent ischemia requiring urgent revascularization; TBO, thrombotic bailout

18

Primary and Key Secondary Efficacy ResultsBy Clopidogrel Strata at Randomization

96-hr Death, MI, RIUR, TBO

Clopidogrel intended 8.8 9.5 0.92 (0.78-1.08)

No Clopidogrel intended 10.8 11.5 0.93 (0.72-1.20)

30-day Death / MI

Clopidogrel intended 10.3 12.0 0.85 (0.73-0.91)

No Clopidogrel intended 13.7 13.4 1.03 (0.81-1.31)

Delayed ProvisionalEptifibatide

Routine Early Eptifibatide

OR (95% CI)

Real life or Impact of Clopidogrel pre treatment

Need for Clopidogrel early treatment

19

BackgroundBackground

• Randomized trials have demonstrated that an Randomized trials have demonstrated that an

invasive strategy is superior to a conservative invasive strategy is superior to a conservative

strategy in NSTE-ACSstrategy in NSTE-ACS

• The optimal timing of intervention remains a The optimal timing of intervention remains a

matter of debatematter of debate

• A “primary PCI” approach of NSTE-ACS A “primary PCI” approach of NSTE-ACS

has not been tested yethas not been tested yet

20

ABOARD study designABOARD study design

NSTE-ACS NSTE-ACS 2 of 3 Criteria: Ischemic symptom, ST-T change, troponin rise2 of 3 Criteria: Ischemic symptom, ST-T change, troponin rise

with TIMI score with TIMI score >> 3 3

Immediate cathImmediate cath Next day cathNext day cath

All PCIs on abciximabAll PCIs on abciximab

1-month Follow-up1-month Follow-up

IVRS RANDOMIZATIONIVRS RANDOMIZATION

21

Individual Ischemic Endpoints at 1 monthIndividual Ischemic Endpoints at 1 month

02468

101214161820

ImmediateDelayed

%%

P=0.28

P=0.09

P=0.32

P=0.57

P=0.62

P=0.08

22

In-hospital medicationsIn-hospital medications

Immediate(N=175)

Delayed(N=177)

Aspirin, (%) 99.4 100

Clopidogrel, (%) 96.6 98.9

Loading dose, mean ± sd, mg 660 ± 268 663 ± 267

Maintenance dose, mean ± sd, mg 111 ± 40 111 ± 39

Abciximab, (%) 65.1 57.4

Unfractionated heparin only, (%) 5.1 3.4

Low Molecular Weight Heparin only, (%) 68.6 67.2

Both UFH and LMWH, (%) 22.9 28.8

Neither UFH nor LMWH, (%) 2.9 0.6

Beta-blocker, (%) 87.4 85.3

Statin, (%) 94.3 95.5

ACE inhibitor or ARB, (%) 84.5 80.2

Optimal adjunctive therapy

23

STEMI/NSTEMI

Clopidogrel 300 or 600 mg?

24

Impact of clopidogrel loading dose on the safety and effectiveness of bivalirudin in patients undergoing primary angioplasty for acute

myocardial infarction: The HORIZONS AMI trial

George Dangas, Giulio Guagliumi, Bernhard Witzenbichler, Deepak Bhatt, Frederick Feit, Magnus Ohman, S. Chiu Wong, Helen Parise,

Roxana Mehran, Gregg W. Stone

25 JACC Sept 2009

26

Baseline Characteristics

  300mg LD 600mg LD P value

Weight (kg) 80.0 [71.0, 90.0]

80.0 [71.0, 90.7]

0.17

BMI (kg/m2)27.1

[24.6, 30.1]27.0

[24.5, 30.3]0.50

Chest pain to ER (hours) 2.2 [1.3, 4.0]

2.2 [1.3, 3.8]

0.45

KILLIP Class 2-4 11.5% 6.9% <.0001

LVEF <40% 15.1% 13.7% 0.28

Femoral a. access 87.3% 96.7% <.0001

Radial a. access 12.4% 2.9% <.0001

Venous access 10.1% 8.0% 0.03

Closure Device 20.3% 33.2% <.0001

Peak ACT (sec) 299.0 [244.0, 379.0]

316.0[254.0, 392.0]

<.0001

IABP 6.5% 4.8% 0.0353

Dangas et al, SCAI-ACCi2 2008

27

Overall: Primary Outcomes (ITT)

*NACE = MACE or major bleeding*NACE = MACE or major bleeding**Not related to CABG**Not related to CABG***MACE = All cause death, reinfarction, ischemic TVR or stroke***MACE = All cause death, reinfarction, ischemic TVR or stroke

P<.0001 P=0.002 P=0.001

Dangas et al, SCAI-ACCi2 2008

28

Study Design, Flow and Compliance

25,087 ACS Patients (UA/NSTEMI 70.8%, STEMI 29.2%)Planned Early (<24 h) Invasive Management with intended PCIIschemic ECG Δ (80.8%) or ↑cardiac biomarker (42%)

25,087 ACS Patients (UA/NSTEMI 70.8%, STEMI 29.2%)Planned Early (<24 h) Invasive Management with intended PCIIschemic ECG Δ (80.8%) or ↑cardiac biomarker (42%)

PCI 17,232(70%)

Angio 24,769(99%)

Angio 24,769(99%) No PCI 7,855

(30%)

No Sig. CAD 3,616 CABG 1,809 CAD 2,430

Randomized to receive (2 X 2 factorial):

CLOPIDOGREL: Double-dose (600 mg then150 mg/d x 7d then 75 mg/d) vs Standard dose (300 mg then 75 mg/d)

ASA: High Dose (300-325 mg/d) vs Low dose (75-100 mg/d)

Efficacy Outcomes: CV Death, MI or stroke at day 30Stent Thrombosis at day 30

Safety Outcomes: Bleeding (CURRENT defined Major/Severe and TIMI Major)Key Subgroup: PCI v No PCI

Efficacy Outcomes: CV Death, MI or stroke at day 30Stent Thrombosis at day 30

Safety Outcomes: Bleeding (CURRENT defined Major/Severe and TIMI Major)Key Subgroup: PCI v No PCI

29

Clopidogrel: Double vs Standard DosePrimary Outcome and Components

Standard Double HR 95% CI P Intn P

CV Death/MI/Stroke

PCI (2N=17,232) 4.5 3.9 0.85 0.74-0.99 0.0360.016

No PCI (2N=7855) 4.2 4.9 1.17 0.95-1.44 0.14

Overall (2N=25,087) 4.4 4.2 0.95 0.84-1.07 0.370

MI

PCI (2N=17,232) 2.6 2.0 0.78 0.64-0.95 0.0120.025

No PCI (2N=7855) 1.4 1.7 1.25 0.87-1.79 0.23

Overall (2N=25,087) 2.2 1.9 0.86 0.73-1.03 0.097

30Days

Cu

mu

lati

ve H

azar

d

0.0

0.01

0.02

0.03

0.04

0 3 6 9 12 15 18 21 24 27 30

Clopidogrel: Double vs Standard Dose Primary Outcome: PCI Patients

Clopidogrel Standard

Clopidogrel Double

HR 0.8595% CI 0.74-0.99

P=0.036

15% RRR15% RRR

CV Death, MI or StrokeCV Death, MI or Stroke

31

ConclusionsASA Dose Comparison

• No significant difference in No significant difference in efficacy or bleeding between efficacy or bleeding between ASA 300-325 mg and ASA 75-ASA 300-325 mg and ASA 75-100 mg.100 mg.

32

J. Mehilli, A. Kastrati, K. Huber, S. Schulz, J. Pache, C.Markwardt, S. Kufner, F. Dotzer, K. Schlotterbeck,

J. Dirschinger, A. Schömig .

Abciximab in Patients with AMI Undergoing Primary PCI After

Clopidogrel Pretreatment

BRAVE-3 TrialBavarian Reperfusion AlternatiVes Evaluation-3 Trial

ClinicalTrials.gov Identifier: NCT00133250

33

Background

Glycoprotein IIb/IIIa inhibitors (GPI) may improve the results of primary PCI in acute STEMI

Pretreatment with a 300mg loading dose of clopidogrel improved the outcome of patients undergoing PCI in the setting of the CLARITY trial

A higher, 600mg loading dose of clopidogrel further enhances and accelerates platelet inhibition

34

Endpoints

Final infarct size (% of the left ventricle)

SPECT study (5-7 days after randomization)

Primary endpoint:

Myocardial perfusion %

100%0% 50%

Secondary endpoints:

Death Myocardial reinfarction Urgent revascularization Stroke Major and minor bleedings (TIMI criteria) Profound thrombocytopenia

35

Clopidogrel 600 mg oral Aspirin 500 mg i.v. or oral

Unfractionated Heparin 5000 IE

Study Therapy(randomized, double-blind, multicenter)

Placebon=399

Abciximabn=401

Aspirin 200mg/day indefinitely Clopidogrel 2 x 75mg/day for 3 days

Clopidogrel 75mg/day for at least 4 weeks

36

Reperfusion Strategy

4 3

48 50

44 44

34

100

60

20

%

Abciximab Placebo

Drug-eluting stents

Bare metal stents

PTCA

Medical treatment

P =.80

37

Primary Endpoint

% LV

Abciximab Placebo

Final infarct sizeMedian [25th; 75th percentile]

Final infarct sizeMean

15,7 16,6

0

10

20

30

40

% LV P = .47

Abciximab Placebo

P =.76

10 9

0

10

20

30

40

38

Conclusion

In patients with acute STEMI undergoing

primary PCI after pre-treatment with a 600mg

loading dose of clopidogrel, the additional use

of abciximab is not associated with further

reduction in infarct size

39

Study Design

Double-blind

ACS (STEMI or UA/NSTEMI) & Planned PCI

ASA

PRASUGREL60 mg LD/ 10 mg MD

CLOPIDOGREL300 mg LD/ 75 mg MD

1o endpoint: CV death, MI, Stroke2o endpoints: CV death, MI, Stroke, Rehosp-Rec Isch

CV death, MI, UTVRStent Thrombosis (ARC definite/prob.)

Safety endpoints: TIMI major bleeds, Life-threatening bleedsKey Substudies: Pharmacokinetic, Genomic

Median duration of therapy - 12 months

N= 13,600

40

Healthy VolunteerCrossover Study

-20-20

00

2020

4040

6060

8080

100100

IPA

at

24 h

ours

(%

)IP

A a

t 24

hou

rs (

%)

Response to Response to Prasugrel 60 mgPrasugrel 60 mg

Response to Response to Clopidogrel 300 mgClopidogrel 300 mg

Clopidogrel ResponderClopidogrel Responder

Clopidogrel Non-responderClopidogrel Non-responder

Inte

rpat

ien

tIn

terp

atie

nt

Var

iab

ilit

yV

aria

bil

ity

Interp

atient

Interp

atient

Variab

ilityV

ariability

From Brandt JT AHJ 153: 66e9,2007

N=66

41

0

5

10

15

0 30 60 90 180 270 360 450

HR 0.81(0.73-0.90)P=0.0004

Prasugrel

Clopidogrel

Days

En

dp

oin

t (%

)

12.1

9.9

HR 1.32(1.03-1.68)P=0.03

Prasugrel

Clopidogrel1.8

2.4

138 events

35 events

Balance of Balance of Efficacy and SafetyEfficacy and Safety

CV Death / MI / Stroke

TIMI Major NonCABG Bleeds

NNT = 46

NNH = 167

42

Net Clinical BenefitDeath, MI, Stroke,

Major Bleed (non CABG)

0

5

10

15

0 30 60 90 180 270 360 450Days

En

dp

oin

t (%

)

HR 0.87P=0.004

13.9

12.2

Prasugrel

ClopidogrelITT= 13,608ITT= 13,608

All CauseAll CauseMortalityMortality

Clop 3.2%Clop 3.2%Pras 3.0 %Pras 3.0 %P=0.64P=0.64

43

B

OVERALL

No GPIGPI

DESBMS

DMNo DM

>7565-74<65

FemaleMale

STEMIUA/NSTEMI

0.5 1 2Prasugrel Better Clopidogrel BetterHR

Age

Reduction in risk (%)18

2112

25146

1430

2018

2116

19

21

Pinter = NS

CV Death, MI, StrokeCV Death, MI, StrokeMajor SubgroupsMajor Subgroups

CrCl > 60CrCl < 60 14

20

44

TRITON-TIMI 38 STEMI cohortTRITON-TIMI 38 STEMI cohort

TRITON allowed recruitment of STEMI patients undergoing primary PCI when they presented < 12 hours of symptom onset or

secondary PCI when they presented late

0

1

2

3

4

5

6

TIMI majorbleed

Lifethreatening

TIMI majoror minor

clopidogrel

prasugrel

P=0.03P=0.03P=0.01P=0.01

P=0.002P=0.002

Wiviott et al.Wiviott et al. New Engl J Med New Engl J Med 2007;357:2001-20152007;357:2001-2015

0

5

10

15

0 30 60 90 180 270 360 450

HR 0.81(0.73-0.90)

Days

CV

Dea

th, M

I, S

trok

e (

%)

12.1

9.9

NNT= 46

Prasugrel

Clopidogrel

P<0.001

45

Primary EP (CV death, MI and stroke at 15 months)

Montalescot et al. ESC 2008

Time (Days)

5

10

15

0

0 50 100 150 200 250 300 350 400 450

Pro

por

tion

of

pat

ien

ts (

%)

9.5

6.5

12.4

10.0

HR=0.79 (0.65–0.97) NNT=42

p=0.02RRR=2

1%p=0.002RRR=32%

Clopidogrel

Prasugrel

Age-adjusted HR=0.81 (0.66-0.99)

STEMI cohort

46

PLATO Lars Vallentin

Perspective ClopidogrelPrasugrelTicagrelor

Albert Schoming Editorial NEJM 2009, 361,11, 1108

Rapidité d’actionVariabilité interindividuelleReversibilitéRisque hémorragiqueEfficacité clinique

47

PLATO study design

6–12 months treatment

PCI = percutaneous coronary intervention; CV = cardiovascular; PI = principal investigator

NSTEMI ACS (moderate-to-high risk) STEMI (if primary PCI) (N=18,624)Clopidogrel-treated or -naive; randomized <24 hours of index event

At randomization, 13,408 (72%) of patients were specified by the Investigator: intent for invasive strategy

Primary endpoint: CV death + MI + Stroke Primary safety endpoint: Total major bleeding

Clopidogrel (n=6,676)If pre-treated, no additional loading dose;if naive, standard 300 mg loading dose,

then 75 mg qd maintenance;(additional 300 mg allowed pre-PCI)

Ticagrelor (n=6,732)180 mg loading dose, then

90 mg bid maintenance;(additional 90 mg pre-PCI)

48

Primary endpoint: CV death, MI or stroke

0

0

5

10

15

60 120 180 240 300 360

Days after randomization

K-M

est

ima

ted

rat

e (%

per

ye

ar)

HR: 0.84 (95% CI = 0.75–0.94), p=0.0025

9.02

10.65Clopidogrel

Ticagrelor

No. at risk

Clopidogrel

Ticagrelor

6,676

6,732

6,129

6,236

6,034

6,134

5,881 4,815

4,889

3,680

3,735

2,965

3,0485,972

K-M = Kaplan-Meier; HR = hazard ratio; CI = confidence interval

49

Primary safety event: Major bleeding*

No. at risk

Clopidogrel

Ticagrelor

6,585

6,651

5,215

5,235

4,984

4,947

4,786

Days after randomization

3,753

3,726

2,754

2,741

2,496

2,503

0 60 120 180 240 300 360

10

5

0

15

Clopidogrel

Ticagrelor

11.6

11.5

4,755

K-M

est

imat

ed r

ate

(% p

er y

ear)

HR 0.99 (95% CI = 0.89–1.10), p=0.88

* PLATO definitions

50

CURE TRITON PLATO

En perspective

Albert Schoming Editorial NEJM 2009, 361,11, 1108

51

A n t ip la t e le t T h e r a p y in A C SA n t ip la t e le t T h e r a p y in A C S

Placebo APTC CURE TRITON-TIMI 38S in g le

A n t ip la t e l e t R xD u a l

A n t ip la t e l e t R xH ig h e r

IP A

A S AA S A +

C lo p id o g r e l A S A + P r a s u g r e l

- 2 2 %

- 2 0 %

- 1 9 %

+ 6 0 % + 3 8 % + 3 2 %

R e d u c t io nin

Is c h e m icE v e n t s

In c r e a s ein

M a jo r B le e d s

52

Les “nouveaux” effets secondaires découverts par PLATO: dyspnée, bradyarythmie, élévation créat, ac urique!!!!!

CURE et TRITON: pas de réduction de la mortalité globale, Ici réduction (mais étude non dimensionnée pour) mais effet très probable.

53

Relative Risk Reduction

PCI No PCI

CURECURE: Clopidogrel 300/75 mg v Placebo (CVD/MI): Clopidogrel 300/75 mg v Placebo (CVD/MI) 30%30%11 19%19%22

STEMI: STEMI: Clopidogrel 300/75 mg v Placebo (CVD/MI)Clopidogrel 300/75 mg v Placebo (CVD/MI) 46%46%33 9%9%44

TRITONTRITON: : Prasugrel v Clopidogrel 300/75mg (CVD/MI/Stroke)Prasugrel v Clopidogrel 300/75mg (CVD/MI/Stroke) 19%19%55Not Not

evaluatedevaluated

PLATO PLATO : Ticagrelor v Clopidogrel 300/75mg (CVD/MI/Stroke): Ticagrelor v Clopidogrel 300/75mg (CVD/MI/Stroke) 16%16%66 15%15%**NSNS

CURRENT : CURRENT : Clopidogrel 600/150 v 300/75mg (CVD/MI/Stroke)Clopidogrel 600/150 v 300/75mg (CVD/MI/Stroke) 15%15%77ddeleterious ?eleterious ?

+17%+17%**p=0.14p=0.14

Benefits of Antiplatelet Therapy in ACS are Greater in Patients Undergoing PCI

1. Mehta SR, et al. Lancet 2001; 358(9281):527-33.2. Fox KAA, et al. Circulation 2004;110:1202-83. Sabatine MS, et al. JAMA 2005; 294(10):1224-32.4. Chen ZM Lancet 2005;366:1607-214. Boersma E et al. Lancet 2002; 359:1895. Wiviott S et al. N Engl J Med 20072007; 357: 2001–15.

6. Wallentin L et al. N Engl J Med 20097. Metha et al. presented at the ESC09

54

STEMIREPERFUSION

Thrombolyse: 300mg ClopidogrelPPCI: Prasugrel 60 mg (si <75 ans et >60 kg, pas d’AVC)PPCI: Clopidogrel 600 mg dans les autres cas.No GP2B3A ( indication au cathlab)

NO REPERFUSION (les oubliés de la repérfusion)Clopidogrel 300 mg

NSTEMIHaut risque : Prasugrel 60 mg(LD)Bas risque: Clopidogrel 300 mg(LD)

+Stratégie Radiale

Thrombo aspiration

+Stratégie Radiale

Thrombo aspiration

STRATEGIE ANTIAGGREGANTE SAMU-USIC DANS LES SCA

STRATEGIE ANTIAGGREGANTE SAMU-USIC DANS LES SCA

Dr D Coisne, Dr J Mergy, Dr L ChristiaensDr D Coisne, Dr J Mergy, Dr L Christiaens

55

Prasugrel 10 mg vs Clopi 150 mg ?Moyen terme

G Montalescot Thrombosis and Haemostasis 2010G Montalescot Thrombosis and Haemostasis 2010

56

57

58

59

60

61

TRILOGY ACS:TRILOGY ACS: TTaaRRgeted platelet geted platelet IInhibition nhibition to cto cLLarify the arify the OOptimal strateptimal strateGGy to medically to medicallYY

manage manage AAcute cute CCoronary oronary SSyndromesyndromes

Protocol SynopsisProtocol Synopsis

62

BB- Objectifs- Objectifs

• Objectif principal:Objectif principal: Etude de supérioritéEtude de supériorité

PrasugrePrasugrel l ++

AspirineAspirine

ClopidogrelClopidogrel++

AspirineAspirine

>

Etude Phase 3, multicentrique, randomisée, double aveugle, Etude Phase 3, multicentrique, randomisée, double aveugle, double placebo, groupes parallèles, contrôlée versus comparateur double placebo, groupes parallèles, contrôlée versus comparateur actif.actif.

Patients éligibles:Patients éligibles: Présentant un évènement UA/NSTEMI récent (au cours des 7 Présentant un évènement UA/NSTEMI récent (au cours des 7 jours précédents) (événement de référence)jours précédents) (événement de référence)Et devant recevoir Et devant recevoir une prise en charge médicamenteuseune prise en charge médicamenteuse..

Etude Phase 3, multicentrique, randomisée, double aveugle, Etude Phase 3, multicentrique, randomisée, double aveugle, double placebo, groupes parallèles, contrôlée versus comparateur double placebo, groupes parallèles, contrôlée versus comparateur actif.actif.

Patients éligibles:Patients éligibles: Présentant un évènement UA/NSTEMI récent (au cours des 7 Présentant un évènement UA/NSTEMI récent (au cours des 7 jours précédents) (événement de référence)jours précédents) (événement de référence)Et devant recevoir Et devant recevoir une prise en charge médicamenteuseune prise en charge médicamenteuse..

63

Conclusion 1

Anti platelets agents.

Rapid and profound anti platelet inhibition is mandatory Oral +/- Parenteral

New Drugs

Anti thrombin agents

We need to look for drugs with maximum efficacy and …..safety.

64

Is It « Aspirin Prasugrel, Bivalirudin », the future very best association in PPCI??

What about Cangrelor associated to Enox or Biva.

More Trials need to be done to give the real place of theses new drugs in the ACS

Conclusion 2