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

Abstract

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.|P[s8|P]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.|P[s8|P]Results Intravenous clopidogrel produced a rapid (within 30min) and dose-dependent inhibition of stent thrombosis, with 87% reduction at a dose of 10mg.kg−1(P<0·001). Aspirin alone (10mg.kg−1) was minimally effective (20% inhibitionP>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 (2·5–5·0mg.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.