Diagnostics for Aspirin Resistance
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Diagnostics for Aspirin Resistance Paul A. Gurbel, Kevin P. Bilden and Udaya S. Tantry Sinai Center for Thrombosis Research, Baltimore, Maryland, USA
The clinical efficacy of aspirin therapy in preventing thrombotic events that has been observed in major clinical trials has mainly been attributed to the inhibition of the platelet cyclo-oxygenase (COX)-1 enzyme. Based on the measurement of stable thromboxane derivatives, it was suggested that more than 95% inhibition of platelet COX-1 is required to observe any clinical efficacy of aspirin therapy.[1] Recently, reports of ‘aspirin resistance’ have emerged and its association with adverse clinical event occurrence has attracted major interest among clinicians as well as the general public.[2] Laboratory methods that isolate the primary target of aspirin in platelets (i.e. inhibition of COX-1 by using arachidonic acid as an agonist in platelet aggregation measurements), have demonstrated that aspirin is highly effective in inhibiting platelet COX-1. However, the estimation of the prevalence of ‘aspirin resistance’ is highly assay-specific, and higher prevalence is significantly associated with methods that do not directly detect the effects of platelet COX-1; i.e. ADP- or collagen-induced aggregation methods and urinary 11-dehydrothromboxane B2 measurements.[3] It is also important to note that aspirin resistance as detected by such COX-1 nonspecific methods has been found to be associated with adverse clinical event occurrence and diabetes mellitus.[4,5] Despite the near uniform inhibition of platelet COX-1 by 81–325 mg daily-dose aspirin, aspirin treatment has been demonstrated to have a dose-dependent effect based on ex vivo COX-1 nonspecific methods.[3] These reports raise important questions regarding the novel non-COX-1 effects of aspirin or extraplatelet sources of thromboxane that may be more pronounced in certain pathological conditions, including diabetes. Moreover, selected patients with high platelet reactivity to various agonists during low-dose aspirin therapy may benefit from higher doses to gain maximum antithrombotic benefits. In order to identify these patients, a simple assay that is relevant to the pathobiology associated with adverse clinical thrombotic events is needed. In this regard, a simple, specific, and more sensitive assay measuring stable urinary thromboxane metabolites may have a clinical impact.
AspirinWorks® is a new ELISA-based diagnostic test developed by Corgenix, Inc. to monitor the effects of aspirin by measuring the stable metabolite of thromboxane A2 (11dehydrothromboxane B2 [11dhTxB2]) in urine. In the HOPE (Heart Outcomes Prevention Evaluation) trial, Eikelboom et al.[6] demonstrated that elevated levels of urinary thromboxane (levels in the upper quartile) were associated with an increased risk of myocardial infarction and cardiovascular death. Recent studies have also confirmed the association of elevated levels of urinary thromboxane with high risk of adve
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