Early healing after carotid endarterectomy: effect of high- and low-dose aspirin on thrombosis and early neointimal hyperplasia in a nonhuman primate model.

Platelet aggregation and release phenomena are central to most postulated mechanisms of thrombosis and neointimal hyperplasia after carotid endarterectomy. Therefore high-dose aspirin (HDA) has been advocated to minimize these sources of endarterectomy failure. We have defined low-dose aspirin (LDA) that selectively blocks platelet cyclooxygenase but preserves arterial wall cyclooxygenase in the nonhuman primate, Macaca fascicularis. We compared this theoretically optimal aspirin dose with HDA and no treatment (control) in a model of carotid endarterectomy. The aspirin was started before operation and continued for 6 weeks after operation, at which time the endarterectomized vessels were excised. The patency and morphologic findings of the arteries were measured. Platelet function was monitored by bleeding time and serum thromboxane A2 determinations. LDA and HDA were associated with 100% patency, whereas the control group had 50% patency. However, HDA did not protect the vessel from developing neointimal hyperplasia, which was seen in the control group and was associated with platelet adherence to the flow surface at 6 weeks. At 6 weeks, LDA significantly decreased but did not totally prevent neointimal hyperplasia and the flow surface was healed. Therefore the genesis of neointimal hyperplasia after endarterectomy may be more complex than simply a function of platelet-vessel wall interaction.