1

Dra. Gemma VilahurCardiovascular Research Center 

IIB‐ HSCSP, UAB, CSIC‐ICCCBarcelona

Diferències en els mecanismes d’acció dels antiagregants. 

Implicacions

Atherosclerosis progressionHealthy vessel

Healthy arteryFatty streak Fibrous 

atheromatous plaque

Plaque ruptureFatty streak progression

Pathophysiology of CVD: aterosclerotic plaque rupture and thrombus formation

ATHEROTHROMBOSISThrombus formation

PAD

CVA Acute coronary syndromes

WORLDWHO 2012CVD: 17,5 million people died from CVDLEADING CAUSE OF DEATH GLOBALLY(31% total) 

2

NSTEMI & UA STEMI

ACS

Acute coronary syndrome: the culprit thrombus

Role of platelet in thrombosis: platelet aggregation and coagulation

G.Vilahur & L. Badimon  Vasc Pharmacol. 2014

L. Badimon & G.Vilahur European Heart Journal (ACC) 2013

Platelet aggregation

Coagulation

3

L. Badimon & G. Vilahur  Eur Heart J ACC 2014

Antiplatelet targets in CAD

PAR

P2Y1

P2Y12

α2

TP

Epinephrin

ATP

P2X1

ADP

ADP

Seroton

in

Thrombin

TXA2

FVW

Fibrinogen

TXA2

AA

PGH2

PGG2

LamininFibronectin

GPIc/IIaGPIa/IIa

GPIb-IX-V

FVW

5-HT2

PLATELET ACTIVATION

PLATELETACTIVATION

PLATELET ACTIVATION

Rc GPIIb/IIIa

Collagen

PAF

Platelet

GPVI

Collagen

AMPc

ADP recptor antagonists

Clopidogrel CangrelorTicagrelor

PrasugrelElinogrelTiclopidine

Subendothelium

PDE inhibitors

DipyridamoleCilostazol

PAR inhibitors

Vorapaxar

Thromboxanereceptor blockade

TerutrobanSulotroban

Aspirin

Thromboxanepathway inhibitors

PDE

Abciximab

GPIIb/IIIa inhibitors

EptifibatideTirofiban

Antiplatelet targets in CAD: aspirin

Arg120

NSAIDS(naproxen,ibuprofen,etc)

Reversibleinteraction

uponaspirinwithdrawal,there‐appearanceofthromboxaneA2biosynthesisfullyrecoversafter

7‐10days

4

γGαqPLC

Ca2+

Platelet SHAPE CHANGE

TRANSIENT plateletaggregation

I3P + DAGPKC

P2Y12 P2Y1

αIIbβ3

L. Badimon & G. Vilahur  Rev Esp Cardiol 2012

ADP‐receptors signaling pathway

ADP

Gi

Active metabolites

Hepaticmetabolism

TICLOPIDINECLOPIDOGRELPRASUGREL

TICAGRELORCANGRELORELINOGREL

γGranules secretion

αβ

PI3K

SUSTAINED platelet aggregation

ACAMPcATP

PKA

VASPVASP-P

PGE1

-

Receptor activation

RBC

Thienopyridines

Ticlopidina Clopidogrel Prasugrel

Primera generación Segunda generación Tercera generación

Administración: oralConversión metabólica: siReversible: noVida media: 30‐50hDuración acción: 5‐10 días

Administración: oralConversión metabólica: siReversible: noVida media: 7hDuración acción: 5‐10 días

Administración: oralConversión metabólica: siReversible: noVida media: 3.5hDuración acción: 5‐10 días

Ticagrelor Cangrelor

Ciclo‐pentil‐triazol‐pirimidine

Análogo del adenosín‐trifosfato

Administración: parenteralConversión metabólica: noReversible: siVida media: 2‐5minDuración acción: 1h

Administración: oralConversión metabólica: noReversible: siVida media: 12hDuración acción:  1día

Elinogrel

Administración: parenteral y oralConversión metabólica: noReversible: siVida media: oral: 12‐14h: parenteral: 50minDuración acción: oral:1 día; parenteral:2h

Sulfonilurea

L.Badimon, G .Mendieta,  G.Vilahur Rev Esp Cardiol 2014

P2Y12 receptor blockers

5

L. Badimon & G. Vilahur  Rev Esp Cardiol 2012

PK and PD of P2Y12 inhibitors

Esterases (90%) 

P2Y12Inactivation 

Clopidogrel(2nd GenerationThienopyridine)

Intermediate metabolyte 

(2‐Oxo‐clopidogrel)

Inactive Metabolyte (SR26334)

Active metabolyte (R‐130964)

CYP 3A 4/5CYP2C9CYP2C19CYP2B6CYP2D6

CYP 1A2CYP2C19CYP2B6

VariabilityLimited efficacyIrreversible

Glycoprotein ‐P

Prasugrel(3rd Generation Thienopyridine)

Hydrolosis by 

esterase

Active metabolyte 

(R‐138727)Inactive metabolyte 

(R‐95913)

CYP 3A 4/5CYP2C19CYP2B6

Limited variabilityHigh efficacyIrreversible

Thienopyridines bind covalently rendering the receptor non‐functional 

for the life of the platelet

ADP

‐20

0

20

40

60

80

100

IPA at 24 hours (%)

Response to Prasugrel 60 mg

Response to Clopidogrel 300 mg

Clopidogrel Responder

Clopidogrel Non‐responder

Interpatient

Variability

Interpatie

nt

Variab

ility

(N=66)

Prasugrel: the most powerful thienopyridine Brandt JT et al. Am Heart J 2007

Healthy Volunteer Crossover Study

6

TRITON TIMI‐38: Balance of SAFETY and EFFICAY

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

CV Death/MI/Stroke

TIMI Major Non-CABG Bleeds

NNT = 46

NNH = 167

Post‐hoc assessments revealed that Prasugrel…

OVERALL

< 60 kg

>=75 years

Yes

0.5 1 2

PriorStroke/TIA

Age

Weight 

Risk (%)

+ 54

‐16

‐1

‐16

+3

‐14

‐13

Clopidogrel BetterHR

Pint = 0.006

Pint = 0.18

Pint = 0.36>=60 kg

< 75 years

No

Prasugrel Better

7

Yang X et al J Cardiovas Pharm & Therap 2013

Clopidogrel Aspirin

Platelet aggregation

30min ischemia + 

3h reperfusion

ClopidogrelAspirin

Pleiotropic effects of P2Y12 antagonists: reduce infarct size

Infarct size

Zhao et al,  Am J Physiol 2003

Post‐conditioning protective effects

Clopidogrel 300mg vs 600 mg: ARMYDA‐6 trial

Primary end‐point : infarct size

2) Improved coronary flow

1) Improved coronary patency

Potential explanations:

8

Prasugrel

(Thienopyridine)

Hydrolosis by 

esterase

Active metabolyte 

(R‐138727)Inactive metabolyte 

(R‐95913)

CYP 3A 4/5CYP2C19CYP2B6

Limited variabilityHigh efficacyIrreversible

L. Badimon & G. Vilahur  Rev Esp Cardiol 2012

Esterases (90%) 

P2Y12Inactivation 

Clopidogrel

(Thienopyridine)

Intermediate metabolyte 

(2‐Oxo‐clopidogrel)

Inactive Metabolyte (SR26334)

Active metabolyte (R‐130964)

CYP 3A 4/5CYP2C9CYP2C19CYP2B6CYP2D6

CYP 1A2CYP2C19CYP2B6

VariabilityLimited efficacyIrreversible

Glycoprotein ‐P

TICAGRELOR: REVERSIBLE INHIBITIONWhen ticagrelor is bound, ADP can still bind but does not induce receptor 

activation

ADP

PK and PD of P2Y12 inhibitors

Active metabolyte(ciclopentil‐triazolopirimidina)No  in vivo 

biotransformation

Ticagrelor

(cyclo‐pentyl‐triazolo‐pyrimidine)

Low variabilityRapid effectHigh efficacyReversible

3‐4dayswithdrawalprevious CABG

PRASUGREL:9dayscompleteplateletrecovery

CLOPIDOGREL7dayscompleteplateletrecovery

0 2 4 6 8 10 12

12

11

109

876

5

4

3210

13

CV

de

ath

, MI

or

stro

ke (

%)

9.8

11.7

HR=0.84; 95% CI=0.77–0.92; p<0.001

Clopidogrel

Ticagrelor

Months after randomisation

Primary composite endpoint

0 2 4 6 8 10 12

6

4

3

2

1

0

Clopidogrel

Ticagrelor

4.0

5.1

HR=0.79; 95% CI=0.69–0.91; p=0.001

7

5

Months after randomisation

Cu

mu

lativ

e in

cid

en

ce (

%)

CV death

Wallentin L, et al. N Engl J Med 2009;361:1045–1057

9

0 2 4 6 8 10 12

12

11109

876

5

43210

13

CV

de

ath

, MI

or

stro

ke (

%)

9.8

11.7

HR=0.84; 95% CI=0.77–0.92; p<0.001

Clopidogrel

Ticagrelor

Months after randomisation

Primary composite endpoint

0 2 4 6 8 10 12

6

4

3

2

1

0

Clopidogrel

Ticagrelor

4.0

5.1

HR=0.79; 95% CI=0.69–0.91; p=0.001

7

5

Months after randomisation

Cu

mu

lativ

e in

cid

en

ce (

%)

CV death

Wallentin L, et al. N Engl J Med 2009;361:1045–1057

STEMI

4.7

6.1

p<0.01 

Myocardial infarction

9.3

11.0

p<0.02 

STEMI

PLATO subanalysis in STEMI patients (Nov 2009; AHA)

Storey RF et al. J Am Coll Cardiol 2010

Maximum LTA response (ADP 20μM) VerifyNow P2Y12 assay

The PLATO PLATELET substudy: Ticagrelor exerts higher antiplatelet effects than clopidogrel

Ticagrelor antiplatelet potential

10

GPIIb/IIIa

Platelet inhibition

ADP

P2Y12

Platelets

TICAGRELOR

Adenosine dependent/independent mechanisms leading to Ticagrelor pleiotropic effects

A1A2aA2bA3

Adenosine receptors

‐ Vasodilation‐ Cardioprotection (post‐conditioning)

‐ Modulation of inflammation

A2A

Antiplatelet effects

Endothelial cells

AMP

CD39(NTPDase‐1)

CD73

ATP

Red Blood Cells

ENT‐1

Red Blood Cells

TICAGRELOR

ADENOSINE

Ticagrelor increases adenosine plasma concentration in ACS patients

↑ Adenosine plasma conc. ↓ RBC adenosine uptake ↑ Risk of apnea

Adenosine dose (ug/kg/min)

Median Borg

value

11

Ticagrelor, does it afford cardioprotection in the setting of acute myocardial infarction? 

TICAGRELOR(LD: 180mg; MD: 90 mb bid)

CLOPIDOGREL(LD:600mg; MD: 75mg)

PLACEBO

LAD

Experimental pig model of closed‐chest acute MI induction and reperfusion

2h / 4h 60min

Outcome

Cardiac functional analysisCardiac anatomical analysis

Molecular studies 

24h

3T ‐ MRI 

G.Vilahur et al. Circulation  2016  

Ticagrelor, reduces edema formation post-MI… via adenosine-dependent mechanisms

Treatment CMR

LV mass (g) Non-treated 70.0 [64.1-73.7] Clopidogrel 72.2 [69.3-74.7] Ticagrelor 70.6 [67.9-74.4] Ticagrelor+8SPT 66.5 [65.0-70.2]

Edema (g LV) Non-treated 23.4 [20.9-31.1] Clopidogrel 21.6 [19.5-25.2] Ticagrelor 16.3 [14.2-19.9]*† Ticagrelor+8SPT 24.6 [22.8-25.3]

Edema (% LV) Non-treated 36.2 [33.9-43.2] Clopidogrel 30.1 [26.6-34.5] Ticagrelor 23.1 [20.2-24.4]*† Ticagrelor+8SPT 36.8 [33.6-39.4]

Infact mass (g LV) Non-treated 22.8 [17.3-25.8] Clopidogrel 15.7 [14.2-16.2]* Ticagrelor 12.0 [10.6-12.9]*† Ticagrelor+8SPT 14.9 [14.6-16.1]*

Necrosis (% LV) Non-treated 31.1 [25.9-39.1] Clopidogrel 20.9 [19.3-22.8]* Ticagrelor 16.4 [15.5-17.9]*† Ticagrelor+8SPT 22.4 [21.8-23.9]*

No-reflow (gr LV) Non-treated 4.6 [2.1-6.0] Clopidogrel 2.0 [1.5-2.8]* Ticagrelor 2.1 [1.8-3.0]* Ticagrelor+8SPT 2.2 [2.0-2.6]*

Treatment CMR

Troponin(ng/mL)

Non-treated 19 [16.5-21.7] Clopidogrel 13.4 [13.0-14.0]* Ticagrelor 10.9 [9.3-11.4]*† Ticagrelor+8SPT 14.2 [12.2-16.1]*

Treatment CMR

LVEF (%) Non-treated 43.0 [42.0-43.6] Clopidogrel 47.2 [45.4-48.2] * Ticagrelor 47.2 [45.4-51.0]* Ticagrelor+8SPT 48.7 [46.6-51.0]*

LVEDV (mL) Non-treated 93.0 [87.6-98.1] Clopidogrel 73.7 [68.9-81.3]* Ticagrelor 77.4 [71.8-89.2]* Ticagrelor+8SPT 84.4 [76.9-86.8]*

LVESV (mL) Non-treated 54.0 [49.2-55.6] Clopidogrel 39.5 [36.3-41.9]* Ticagrelor 39.2 [37.3-46.0]* Ticagrelor+8SPT 44.2 [40.4-45.7]*

* p<0.05 vs placebo-control animals† p<0.05 vs clopidogrel-treated animals

G.Vilahur et al. Circulation  2016  

12

Treatment CMR

LV mass (g) Non-treated 70.0 [64.1-73.7] Clopidogrel 72.2 [69.3-74.7] Ticagrelor 70.6 [67.9-74.4] Ticagrelor+8SPT 66.5 [65.0-70.2]

Edema (g LV) Non-treated 23.4 [20.9-31.1] Clopidogrel 21.6 [19.5-25.2] Ticagrelor 16.3 [14.2-19.9]*† Ticagrelor+8SPT 24.6 [22.8-25.3]

Edema (% LV) Non-treated 36.2 [33.9-43.2] Clopidogrel 30.1 [26.6-34.5] Ticagrelor 23.1 [20.2-24.4]*† Ticagrelor+8SPT 36.8 [33.6-39.4]

Infact mass (g LV) Non-treated 22.8 [17.3-25.8] Clopidogrel 15.7 [14.2-16.2]* Ticagrelor 12.0 [10.6-12.9]*† Ticagrelor+8SPT 14.9 [14.6-16.1]*

Necrosis (% LV) Non-treated 31.1 [25.9-39.1] Clopidogrel 20.9 [19.3-22.8]* Ticagrelor 16.4 [15.5-17.9]*† Ticagrelor+8SPT 22.4 [21.8-23.9]*

No-reflow (gr LV) Non-treated 4.6 [2.1-6.0] Clopidogrel 2.0 [1.5-2.8]* Ticagrelor 2.1 [1.8-3.0]* Ticagrelor+8SPT 2.2 [2.0-2.6]*

Treatment CMR

Troponin(ng/mL)

Non-treated 19 [16.5-21.7] Clopidogrel 13.4 [13.0-14.0]* Ticagrelor 10.9 [9.3-11.4]*† Ticagrelor+8SPT 14.2 [12.2-16.1]*

Treatment CMR

LVEF (%) Non-treated 43.0 [42.0-43.6] Clopidogrel 47.2 [45.4-48.2] * Ticagrelor 47.2 [45.4-51.0]* Ticagrelor+8SPT 48.7 [46.6-51.0]*

LVEDV (mL) Non-treated 93.0 [87.6-98.1] Clopidogrel 73.7 [68.9-81.3]* Ticagrelor 77.4 [71.8-89.2]* Ticagrelor+8SPT 84.4 [76.9-86.8]*

LVESV (mL) Non-treated 54.0 [49.2-55.6] Clopidogrel 39.5 [36.3-41.9]* Ticagrelor 39.2 [37.3-46.0]* Ticagrelor+8SPT 44.2 [40.4-45.7]*

* p<0.05 vs placebo-control animals† p<0.05 vs clopidogrel-treated animals

8‐SPT

Ticagrelor, reduces edema formation post-MI… via adenosine-dependent mechanismsG.Vilahur et al. Circulation  2016  

24

Pla

ceb

o-c

on

tro

lC

lop

ido

gre

lT

icag

relo

r

Necrosis (DE) Edema (T2 STIR)

Tic

agre

lor+

8SP

T

Histopathology

Edema(grLV)

CMRInfarctm

assLV(g)

Y=1.657+0.663*X;r=0.74

Placebo‐controlClopidogrelTicagrelor

Ticagrelor+8SPT

0

5

10

15

20

25

30

35

0 5 10 15 20 25 30 35

*†

0

5

10

15

20

25

30

35

Edem

a(grLV)

Ticagrelor reduces infarct size to a greater extent than clopidogrel and edema formation post-MIG.Vilahur et al. Circulation  2016  

13

Molecular analysis related to myocardial edema formation: AQUAPORIN‐4

Aquaporinproteinsaretransmembranechannelscriticallyinvolvedincellularwaterbalanceclosely

relatedtoedemaAquaporin-4 (AQP-4)?

Aquaporin-4 is responsible or cerebral ischemia (Yao et al 2014)

Aquaporin-4 increases after myocardial ischemia and is involved in myocyte swelling and infarct size (Rutkovskiy A et al 2012; Warth et al 2007)

Adenosine signaling regulates aquaporin-4 expression (Lee et al 2013)

Aquaporin-4 expression is found to be reduced in ENT-1-/-

mice (Hinton et al 2014)

G.Vilahur et al. Circulation  2016  (In press)

Aquaporin4

Ischemic

Aquaporin4/β‐actin(AU)

Aquaporin-4 protein levels

Ticagrelor

Placebo‐control

Clopidogrel

Remote

Ticagrelor

Placebo‐control

Clopidogrel

β‐actin

Aquaporin‐4/18SrRNA

Aquaporin-4 mRNA

0

2

4

6

8

10

12

Ticagrelor+8SPT

Ticagrelor+8SPT

* *

0

5

10

15

20

Ticagrelor

Placebo‐control

Clopidogrel

Ticagrelor+8SPT

Ticagrelor

Placebo‐control

Clopidogrel

Ticagrelor+8SPT

Ischemic Remote

Molecular analysis related to myocardial edema formation: AQUAPORIN‐4G.Vilahur et al. Circulation  2016  (In press)

14

Molecular  analysis related to myocardial edema formation: AMPK

0

2

4

6

8

10

12

14

AMPK/β‐actin(AU)

P-AMPK

0

2

4

6

8

10

12

14

P‐AMPK/β‐actin(AU)

AMPK

*

Ticagrelor

Placebo‐control

Clopidogrel

Ticagrelor+8SPT

Ticagrelor

Placebo‐control

Clopidogrel

Ticagrelor+8SPT

Ischemic RemoteTicagrelor

Placebo‐control

Clopidogrel

Ticagrelor+8SPT

Ticagrelor

Placebo‐control

Clopidogrel

Ticagrelor+8SPT

Ischemic Remote

Castanares‐ZapateroDetal.2013

AMPK‐/‐mice:AMPKpreventsventricularedemaformation

G.Vilahur et al. Circulation  2016  

Ticagrelor induces cox2 activation and consequent

prostacyclin release

Pg/

mL

6KetoPGF1αCox2 activity

Pg/

mL

*

0

1000

2000

3000

4000

5000

*

0

2000

4000

6000

8000

10000

12000

14000

Ischemic

Tic

agre

lor

Pla

cebo

-con

trol

Clo

pido

grel

Tic

agre

lor+

8SP

T

Ischemic

Tic

agre

lor

Pla

cebo

-con

trol

Clo

pido

grel

Tic

agre

lor+

8SP

T

Arachidonic Acid

Cox2

PGH2

Endothelialcells

PGI2

Prostacyclinsynthase

Metabolyte 6-keto-PGIα

VASODILATIONANTIPLATELET EFFECTS

G.Vilahur et al. Circulation  2016  

15

P2Y12

Platelet

• Vasodilation• Cardioprotection• Modulation inflammation

A2A

Antiplatelet effects

ENT‐1

Red blood cells

ADENOSINEISCHEMIA

Adenosine Rc

TicagrelorGPIIb/IIIa ADP

CORONARY THROMBOSIS

Off‐targeteffects

ACS‐STEMI

DirectCardioprotection

Ischemicmyocardium

INFARCT SIZE

EDEMA

AMPK sign.

Aquaporin‐4

3T‐CMR

Cox2 – PGI2

G.Vilahur et al. Circulation  2016  

In line with our observations…

Several recent studies have proposed that activated AMPK protects against sepsis‐induced organ damage and inflammation.Escobar DA et al J Surg Res 2015

The post‐hoc analysis of the PLATO trial showed the ticagrelor‐associated reduction insepsis mortality in ACS patients.Storey RF, et al Platelets. 2014

Ticagrelor‐related increase in myocardial COX2 activity may contribute to explainticagrelor benefits reported long after MI in PEGASUS patients.Bonaca MP, et al JAMA Cardiol. 2016;

16

31

ALL GROUPS ORAL TREATMENTMaintenance doses

CMR analysis at 3days and 42 days

Global analysisRegional analysis

ACUTE CARDIOPROTECTION. DOES IT TRANSLATE INTO A BETTER REMODELING PROCESS AND IMPROVED CARDIAC PERFORMANCE AT LONG-TERM?

32

0

5

10

15

20

25

30

35

40

45

50

Edema (gr) No reflow (gr)

3days post-MI

Control

Clopidogrel

Ticagrelor

†

**

gr

LV

*

EDEMA 3 DAYS POST-MI

0

5

10

15

20

25

30

35

Sca

r si

ze (

% L

V)

3days post-MI 42days post-MI

†*

*

†*

SCAR SIZE (3DAYS & 42 DAYS)

TICAGRELOR REDUCES EDEMA AND SCAR SIZE 3 DAYS POST-MI

17

0

20

40

60

80

100

120

140

160

LVEDV LVESV LVEF LVEDV LVESV LVEF

3days post-MI 42days post-MI

Control

Clopidogrel

Ticagrelor

TICAGRELOR IMPROVES CARDIAC FUNCTION AT 3 DAYS POST-MI, AN EFFECTS THAT PERSISTS UP TO 42 DAYS

20

25

30

35

40

45

50

55

60

65

LV

EF

(%

) 3d

ays

po

st-M

I

P<0.05

0

LVEF – 3DAYS

*

mL

or

%

§

§§

§

§

§

*

CARDIAC PERFORMANCE

Impact of ticagrelor on cardiac remodeling: regional analysis

34

Coronary irrigation of the LV

18

35

Ticagrelor improves the Wall motion of the infarcted segments

0

0,5

1

1,5

2

2,5

3

3,5

4

Day 3 post-MI Day 42 post-MI

Control

Clopidogrel

Ticagrelor

P<0.05

Wal

l Mo

tio

n (

mm

)

P<0.05

P=0.05

WALL MOTION

Ticagrelor limits remote remodeling

36

0

0,5

1

1,5

2

2,5

3

3,5

4

Day 3 post-MI Day 42 post-MI

Control

Clopidogrel

Ticagrelor

Wal

l Mo

tio

n (

mm

)

P<0.05

P<0.002

WALL MOTION

19

37

TICAGRELOR ACTIVATES AMPK AT LONG TERM IN THE ENTIRE MYOCARDIUM

0

50

100

150

200

250

AM

PK

(A

U)

AMPK

0

50

100

150

200

250

300

350

300

350

0

1

2

3

4

5

6

7

8C

lopi

dog

rel

Tic

agre

lor

Con

trol

Clo

pido

gre

l

Tic

agre

lor

Con

trol

Clo

pido

gre

l

Tic

agre

lor

Con

trol

P-AMPK P-AMPK/AMPK

*

*

INFARCTED MYOCARDIUM

0

50

100

150

200

250

AM

PK

(A

U)

0

50

100

150

200

250

300

350

300

350

0

1

2

3

4

5

6

7

8

Clo

pido

gre

l

Tic

agre

lor

Con

trol

Clo

pido

gre

l

Tic

agre

lor

Con

trol

Clo

pido

gre

l

Tic

agre

lor

Con

trol

AMPK P-AMPK P-AMPK/AMPK

**

REMOTE (NON-INFARCTED) MYOCARDIUM

†

†

†

TICAGRELOR ACTIVATES AMPK AT LONG TERM IN THE ENTIRE MYOCARDIUM

20

39

G. Vilahur, M. Gutiérrez, L. Casaní, C. Lambert, G. Mendieta, S. Ben-Aicha, A. Capdevila, G. Pons-Lladó, F. Carreras, L.Carlsson,

A. Hidalgo, L. Badimon

Ticagrelor improves cardiac function and post-myocardial infarction healing in a preclinical model: Cardiac magnetic resonance imaging assessment of functional, anatomical and remodeling parameters

Submitted March 2017

L. Badimon & G. Vilahur  Eur Heart J ACC 2014

Antiplatelet targets in CAD

PAR

P2Y1

P2Y12

α2

TP

Epinephrin

ATP

P2X1

ADP

ADP

Seroton

in

Thrombin

TXA2

FVW

Fibrinogen

TXA2

AA

PGH2

PGG2

LamininFibronectin

GPIc/IIaGPIa/IIa

GPIb-IX-V

FVW

5-HT2

PLATELET ACTIVATION

PLATELETACTIVATION

PLATELET ACTIVATION

Rc GPIIb/IIIa

Collagen

PAF

Platelet

GPVI

Collagen

AMPc

ADP recptor antagonists

Clopidogrel CangrelorTicagrelor

PrasugrelElinogrelTiclopidine

Subendothelium

PDE inhibitors

DipyridamoleCilostazol

PAR inhibitors

Vorapaxar

Thromboxanereceptor blockade

TerutrobanSulotroban

Aspirin

Thromboxanepathway inhibitors

PDE

Abciximab

GPIIb/IIIa inhibitors

EptifibatideTirofiban

21

Prof. Lina Badimon

Laura CasaníManuel GutiérrezTeresa PadróJudit CubedoSandra CaminoGuiomar Mendieta

Pablo CatalinaMari CanovasJosep MorenoFrancisco J Rodriguez

Gràcies

Antoni CapdevilaGuillem Pons-LladóAlberto HidalgoFrancesc Carreras

Ricart CullelIngrid Blanca Yela