No effect of clopidogrel activity or cessation on vascular function or markers of inflammation.

The platelet adenosine diphosphate (ADP)-receptor blocker clopidogrel is effective in reducing the rate of thrombosis in cardiovascular disease, but may also have nonplatelet activity. However, there is variability in the suppression of platelet function in individuals, leading to the concept of clopidogrel resistance, that is, reduced platelet-suppressing activity. We tested the hypothesis that some of the beneficial effect of clopidogrel may be due to the variable activity of this drug on the vascular system (assessed by plasma markers von Willebrand factor and soluble E-selectin, and functional arterial pulse wave velocity) and inflammation (C-reactive protein and interleukin-6) while 32 patients with coronary artery disease taking 75 mg clopidogrel daily, and again 2 weeks after cessation of clopidogrel therapy. Platelet responsiveness to clopidogrel was assessed by the phosphorylation of intracellular regulatory protein-vasodilator-stimulated phosphoprotein method and aggregometry to ADP. Response to aspirin was assessed using arachidonic acid (AA), and soluble P-selectin and PAC-1 were also measured. While on clopidogrel, there were no relationships between any vascular or inflammatory index and the response to clopidogrel. After stopping clopidogrel, there were no differences in platelet aggregation to AA, or the expression of P-selectin or PAC-1 at rest, or after stimulation by AA, but platelet responses to ADP all increased (p < 0.01). Although soluble P-selectin increased when clopidogrel was stopped (p = 0.006), there were no changes in plasma markers or vascular function. We conclude that 75 mg/day clopidogrel has no effect of markers of vascular function or inflammation.