Antiplatelet therapy after implantation of drug-eluting stents: duration, resistance, alternatives, and management of surgical patients.
The routine off-label use of drug-eluting stents (DESs) has been associated with a higher prevalence of stent thrombosis in clinical practice than was suggested in US Food and Drug Administration (FDA) preapproval studies. Consequently, the early identification of patients at risk for stent thrombosis has become a major goal in cardiology. Although a number of factors may be involved in DES thrombosis, the biologic cascade begins with local platelet activation and culminates in platelet aggregation, the generation of coagulation factors, the formation of a fibrin network, and the creation of a stable occlusive thrombus. Current data show that the premature discontinuation of dual-antiplatelet therapy is an important risk factor for DES thrombosis, but the occurrence of stent thrombosis in patients adhering to this drug regimen suggests that some patients are nonresponsive to clopidogrel therapy, primarily because of functional and genetic variability in the cytochrome P450 enzymes. Patients with high platelet reactivity to adenosine diphosphate (ADP) during dual-antiplatelet therapy may be at increased risk for adverse ischemic events, including stent thrombosis. Using a point-of-service assay, Price et al measured platelet function in patients treated with DESs and demonstrated that 75% of patients who developed stent thrombosis were in the lowest quartile of platelet inhibition and the highest quartile of platelet reactivity. Data from the authors' center suggest that there may be a threshold of platelet reactivity, as measured by light-transmittance aggregometry after ADP stimulation, that predicts an increased risk for stent thrombosis. Large prospective studies designed to identify which patients are at risk for stent thrombosis on the basis of platelet function testing are under way and may eventually lead to personalized antithrombotic therapy.
Gurbel, PA; DiChiara, J; Tantry, US
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