Effects of clopidogrel, aspirin and combined therapy in a porcine ex vivo model of high-shear induced stent thrombosis

Aims 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). Conclusion Clopidogrel, either alone or combined with aspirin, may have a potential role in preventing stent thrombosis in high-risk clinical situations.