Clopidogrel

(platelets aggregation)(thrombus)
fibrin
(plug)
plug
plug
plug
plug plug
plug

(antiplatelets drug)
Aspirin

Aspirin cyclooxygenase
arachidonic acid Thromboxane A2 (TXA2) TXA2
Thromboxane A2
Aspirin
(bleeding) Antiplatelet
Trialistss Collaoration(ATC) Aspirin 75 mg

(Thrombus)

Prostacyclin Nitric Oxide(NO)
(Endothelial cell) Endothelial cell CD39
adenosine diphosphate(ADP
) adenosine monophosphate(AMP) a

 Subendothelial cell receptor

glycoprotein Ib-IX (GP Ib-IX), integrin 21 ,integrin 51 Von
Willebrand factor ,collagen Fibronectin b Thrombin ADP
(active form) c
ADP,platelets-derived growth factor(PDGF),Fibrinogen
TXA2 ADP TXA2
d
ADP TXA2 Glycoprotein IIb/IIIa receptor
Fibrinogen e
fibrin (Thrombus) f

1
2

1.Phospholipase A2 inhibitor
2.Cyclooxygenase inhibitor
3.Thromboxane synthetase inhibitor
4.Thromboxane receptor antagonist
5.Thromboxane synthetase inhibitor and
Thromboxane receptor antagonist
6.Platelet-receptor antagonists
6.1 Platelet-ADP-receptor antagonist
6.2 Platelet Glycoprotein IIb/IIIa receptor antagonist
- monoclonal antibody
- peptide
- peptidomimetic
7. cAMP phosphodiesterase inhibitor
8. Adenyl cyclase stimulators
9. Miscellaneous

: corticosteroid
: aspirin,NSAIDs
: imidazole,dazoxiben,OKY-1581
: sulotroban,daltroban,vapiprost
: ridogrel,picotamide
: ticlopidine,clopidogrel
: abciximab
: eptifibatide
: tirofiban, lamifiban
: dipyridamole,cilostazol
: PGE1,PGD2,PGI2
: eicosapentaenoic acid

Clopidogrel (Plavix)
Clopidogrel Ticlopidine Thienopyridine
ADP-receptor (irreversible)
Clopidogrel Ticlopidine (
Ticlopidine neutropenia)
ADP ADP
TXA2 Glycoprotein IIb/IIIa receptor Fibrinogen
Clopidogrel ADP-receptor
ADP

Clopidogrel P2Y12 receptor subtype ADP receptor
2

33

 2 receptor
Clopidogrel

CAPRIE

19,185

CREDO
CURE

2,116
12,562

PCI-CURE

2,658

Primary myocardial infarction,stroke,peripheral arterial

disease
Percutaneous coronary intervention
Unstable angina,non-ST-segment elevation myocardial
infarction
Subset of CURE undergoing percutaneous coronary
intervention

CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events)

trial 19,185
384 clopidogrel ( 75 mg)
aspirin( 325 mg) 35
ischemic stroke 6 1

1.6 ( 3 ) clopidogrel
ischemic stroke ,
aspirin clinical endpoint
clopidogrel aspirin
(clopidogrel = 9.78% aspirin = 10.64%) clopidogrel
(bleeding) aspirin
neutropenia thrombocytopenia clopidogrel

 CAPRIE clopidogrel aspirin

revascularization,
clopidogrel
aspirin 2
coronary stenting clopidogrel aspirin
aspirin aspirin warfarin

clopidogrel

ACTIVE
ARCH
CAMPER
CASPAR
CHRISMA
CLARITY
COMMIT
MATCH
WATCH

14,000
15,000
2,000
1,460
15,200
2,200
40,000
7,600
1,587

Atrial fibrillation
Aortic arch atheroma
Peripheral arterial intervention
Peripheral arterial bypass surgery
Secondary and high-risk primary prevention
Acute ST-segment elevation myocardial infarction
Acute ST-segment elevation myocardial infarction
High-risk recent transient ischemic attack or stroke
Heart failure

Clopidogrel
Clopidogrel 75 mg
prodrug 2-oxo-clopidogrel
CYP2B6 3A4 thiol derivative P2Y12
receptor
Clopidogrel Clopidogrel 98% 94%
50% 46%
8

Clopidogrel 75 mg
aspirin
(neutropenia 4 ) , aplastic anemia( 1 ) , , , ,,

1. ..
. 2.:(1996) ;2543 :44-52.
2.Deepak L. Bhatt and Eric J. Topol. Scientific and therapeutic advances in antiplatelet therapy. Nature review Drug discovery.
January 2003 volume 2 no.1:15-28.