Effects of clopidogrel, aspirin and combined therapy in a porcine ex vivo model of high-shear induced stent thrombosis.
OBJECTIVE
Use of ticlopidine in coronary stenting is limited by delayed onset of action. We studied the effects of clopidogrel, a rapidly acting analog of ticlopidine alone, and in combination with aspirin, in inhibiting stent thrombosis.


METHODS
Unpolished nitinol stents were deployed in a porcine ex vivo arteriovenous shunt and exposed to flowing arterial blood at a shear rate of approximately 1500. s-1. Stent thrombus, platelet aggregation and bleeding times were measured at baseline and after treatment.


RESULTS
Intravenous clopidogrel produced a rapid (within 30 min) and dose-dependent inhibition of stent thrombosis, with 87% reduction at a dose of 10 mg.kg-1 (P < 0.001). Aspirin alone (10 mg.kg-1) was minimally effective (20% inhibition P > 0.05) in inhibiting stent thrombosis. Combined treatment with clopidogrel and aspirin produced 95-98% inhibition of stent thrombosis, even at low doses of clopidogrel (2.5-5.0 mg.kg-1) (P < 0.0001). At effective doses both clopidogrel and combined therapy produced significant prolongation of bleeding time (P < 0.05) and inhibition of platelet aggregation (P < 0.05).


CONCLUSIONS
Clopidogrel, either alone or combined with aspirin, may have a potential role in preventing stent thrombosis in high-risk clinical situations.
Makkar
R R
RR
Department of Medicine, Burns and Allens Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Eigler
N L
NL
Kaul
S
S
Frimerman
A
A
Nakamura
M
M
Shah
P K
PK
Forrester
J S
JS
Herbert
J M
JM
Litvack
F
F
D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006083:Graft Occlusion, Vascular / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015607:Stents; D013552:Swine; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin