Enhanced Shear-Induced Platelet Aggregation in Patients Who Experience Subacute Stent Thrombosis

Ajzenberg, Nadine; Aubry, P; Huisse, Marie-Geneviève; Cachier, Agnès; Amara, W.; Feldman, Laurent J.; Himbert, Dominique; Baruch, Dominique; Guillin, Marie‐Claude; Steg, Philippe Gabriel

doi:10.1016/j.jacc.2004.10.079

Cited by 137 publications

(92 citation statements)

References 19 publications

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“…Platelet function tests have been used to monitor patient response to antiplatelet therapy [34]. Several studies suggest that low responsiveness to antiplatelet therapy, as measured in various platelet-function tests, correlates with high rates of incidences of ischemic events [34][35][36][37]. However, it is questionable whether the resistance defined by various platelet-function tests is actually paralleled by the occurrence of adverse clinical events.…”

Section: Discussionmentioning

confidence: 99%

Determination of the Prevalence of Aspirin and Clopidogrel Resistances in Patients with Coronary Artery Disease by using Various Platelet-function Tests

Woo

Kim

et al. 2010

Ann Lab Med

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Patients undergoing percutaneous coronary intervention (PCI) for coronary artery disease (CAD) are administered antiplatelet therapy to reduce the rate of incidence of major adverse cardiac events [1,2]. Dual antiplatelet therapy with aspirin and clopidogrel has emerged as the gold standard treatment for patients treated with drugeluting stents (DES) for the prevention of stent thrombosis [2][3][4]. However, there is variability in the patients' response to antiplatelet therapy, and some patients continue to have ischemic recurrences, including stent thrombosis [2,5]. Although, the pathophysiology of recurrent ischemic events is multifactorial, resistance to aspirin and clopidogrel, which has been reported in a significant Background: Dual therapy with aspirin and clopidogrel has emerged as the gold standard therapy for patients treated with drug-eluting stents (DES). However, there is variability in patients' responses to this antiplatelet therapy, and some patients continue to show ischemic recurrences after therapy. The purpose of the study was to compare the simultaneously obtained results of various plateletfunction tests for assessing the prevalence of antiplatelet resistance in coronary artery disease patients undergoing DES therapy.Methods: A total of 66 patients were administered a loading dose of aspirin, clopidogrel, and cilostazol at least 12 hr before stenting. The results of VerifyNow (Accumetrics, USA), multiplate analyzer (Dynabyte Medical, Germany), and vasodilator-stimulated phosphoprotein/P2Y12 (Biocytex, France) assays were compared with those of light transmission aggregometry (LTA) analysis.Results: The P2Y12 reaction units and P2Y12% inhibition values obtained using the VerifyNow assay showed strong correlation (r) with the results of the LTA analysis. All tests results showed low concordance in defining the antiplatelet resistance in patients, and the degrees of agreement were as follows: 0 for aspirin reaction units; 0.25, P2Y12% inhibition; 0, aspirin-sensitive patients' identification test; 0.21, ADPtest; and 0.14, platelet reactivity index, expressed as the k statistics. The prevalence of aspirin and clopidogrel resistances in patients resulted in remarkable variations, from 0% to 22.7% and from 9.1% to 48.5%, respectively.Conclusions: The clinical usefulness of the different assays for the correct classification of patients in terms of antiplatelet resistance remains unclear. Further studies are required to determine the best method for correlating the occurrences of adverse ischemic events. (Korean J Lab Med 2010; 30:460-8)

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Section: Discussionmentioning

confidence: 99%

Determination of the Prevalence of Aspirin and Clopidogrel Resistances in Patients with Coronary Artery Disease by using Various Platelet-function Tests

Woo

Kim

et al. 2010

Ann Lab Med

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“…This may explain why stent thrombosis occurs only in selected patients after clopidogrel withdrawal. The observation that patients with diabetes frequently have suboptimal response to aspirin may also be implicated in their increased thrombotic event rate, which has been invoked as a potential mechanism leading to stent thrombosis occurring even after 1 year of clopidogrel treatment (21)(22)(23)(24)(25). Several mechanisms lead to reduced responsiveness to aspirin and increased platelet reactivity in diabetic patients, including increased platelet exposure to ADP (21).…”

Section: Discussionmentioning

confidence: 99%

“…The prognostic implications associated with increased platelet reactivity and enhanced inflammatory status, which include progression of atherosclerotic disease and atherothrombotic complications, underscores the potential clinical impact of these functional findings (23)(24)(25)(35)(36)(37)(38)(39). The influence of clopidogrel on inflammatory markers and platelet biomarkers and how these may affect long-term clinical outcomes is currently being evaluated in a large-scale randomized clinical trial.…”

Section: Discussionmentioning

confidence: 99%

Clopidogrel Withdrawal Is Associated With Proinflammatory and Prothrombotic Effects in Patients With Diabetes and Coronary Artery Disease

et al. 2006

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Inhibition of the P2Y 12 pathway by the platelet antagonist clopidogrel is associated with a marked reduction in platelet reactivity. Recent reports have shown that P2Y 12 inhibition has anti-inflammatory effects as well. However, whether clopidogrel withdrawal is associated with proaggregatory and proinflammatory effects has not yet been explored. Since diabetic subjects are characterized by a prothrombotic and proinflammatory status, we hypothesize that these patients may be more vulnerable to these effects. A total 54 patients with diabetes on long-term (12 months) dual antiplatelet therapy (aspirin plus clopidogrel) were studied. Platelet aggregation (following 6 and 20 mol/l ADP stimuli) and inflammatory markers (Creactive protein and P-selectin expression) were assessed before and 1 month following clopidogrel withdrawal. Following clopidogrel withdrawal, aspirin responsiveness using platelet function analyzer-100 was determined as well. A significant increase in all the assessed platelet (P < 0.0001 for 6 and 20 mol/l ADP-induced aggregation) and inflammatory (P < 0.05 for C-reactive protein, P < 0.001 for P-selectin expression in resting platelets, and P < 0.0001 for P-selectin expression in ADP-stimulated platelets) biomarkers was observed following clopidogrel withdrawal. Low responders to aspirin had increased platelet aggregation profiles (P < 0.05 for 6 and 20 mol/l ADPinduced aggregation) but no differences in inflammatory markers. In conclusion, clopidogrel withdrawal is associated with an increase in platelet and inflammatory biomarkers in diabetic patients, supporting pleiotropic effects coupled with P2Y 12 receptor antagonism. Diabetes 55: 780 -784, 2006

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“…10 However, discrepancy exists as to whether clopidogrel resistance correlates with stent thrombosis. In a study of 23 patients, Wenaweser et al found that aspirin and clopidogrel resistance, but not clopidogrel resistance alone, predicted a history of stent thrombosis.…”

Section: Discussionmentioning

confidence: 99%

A case report of simultaneous thrombosis of two coronary artery stents in association with clopidogrel resistance

Lee

Dunn

Marshall

et al. 2007

Clinical Cardiology

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SummaryDespite aggressive antiplatelet therapy in the setting of PCI, the incidence of acute stent thrombosis remains approximately 0.5-2%. We report a patient with simultaneous thrombosis of two drug-eluting coronary artery stents, suggesting a systemic thrombotic state. Evaluation by optical platelet aggregometry revealed clopidogrel resistance, which was overcome at a higher drug dose. We aim to highlight the potential utility of platelet function analysis to guide therapy for patients in whom inadequate antiplatelet therapy may have catastrophic clinical outcomes.

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Enhanced Shear-Induced Platelet Aggregation in Patients Who Experience Subacute Stent Thrombosis

Cited by 137 publications

References 19 publications

Determination of the Prevalence of Aspirin and Clopidogrel Resistances in Patients with Coronary Artery Disease by using Various Platelet-function Tests

Determination of the Prevalence of Aspirin and Clopidogrel Resistances in Patients with Coronary Artery Disease by using Various Platelet-function Tests

Clopidogrel Withdrawal Is Associated With Proinflammatory and Prothrombotic Effects in Patients With Diabetes and Coronary Artery Disease

A case report of simultaneous thrombosis of two coronary artery stents in association with clopidogrel resistance

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