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Anti-Platelet Therapy and Aspirin Resistance - Clinically and Chemically Relevant?

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Platelets play a central role in the pathogenesis of the atherothrombosis which ultimately causes myocardial infarction, stroke and peripheral vascular disease. Commonly used oral anti-platelet drugs include aspirin (an irreversible inhibitor of cyclo-oxygenase), clopidogrel (an ADP receptor antagonist), other thienopyridines such as ticlopidine and prasgruel, and dipyridamole (an inhibitor of adenosine reuptake and platelet phosphodiesterase). Newer agents are in development and one, ticagrelor, a reversible ADP receptor antagonist has shown promise. Despite their proven benefit, recurrent vascular events still occur in those taking anti-platelet drugs. This has led to the concept of anti-platelet resistance, most commonly aspirin resistance as this drug is the cornerstone of most regimens. The causes of aspirin resistance are numerous but potential mechanisms include lack of patient adherence, non COX-1 mediated thromboxane A2 synthesis, increased activity of alternate platelet activation pathways, interference of aspirin action by other drugs and probably pharmacogenetic factors. Measurement of platelet response to aspirin is made possible using a number of in-vitro laboratory assays of platelet function which include measurement of thromboxane A2 metabolites as well as newer point-of-care assays of platelet aggregation. The phenomenon of aspirin resistance is important as it raises the possibility of developing strategies to identify those who respond best to a particular anti-platelet regimen, or to development of newer anti-platelet therapies to which more patients respond. This review discusses important aspects of aspirin resistance both in terms of clinical medicine, alternative anti-platelet strategies, and the potential to overcome its various causes.

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Keywords: Anti-platelet; Arachidonic acid; Light transmittance aggregometry; Polymorphisms; Thienopyridines; Thromboelastography; acetylsalicylic acid; adenosine diphosphate; antiplatelet therapies; arachidonic acid; aspirin; atherosclerotic disease; atherothrombotic disease; cardiovascular risk; clopidogrel; coronary syndrome; cyclic-adenosine monophosphate (cAMP); cyclic-guanosine monophosphate (cGMP); cyclooxy-genase 1; cyclooxygenase enzyme; cyclopentyl-triazolopyrimidine; dipyridamole; electrode platelet ag-gregometry; fibrinogen receptors; glycoprotein; haematopoetic stem cell; haemostasis; liquid chromatography; megakaryocytes; mucosal hydrolysis; myocardial in-farction; myocardial infarction; plasma salicylic acid; platelet-glycoprotein; prasgruel; pre-cipitate stroke; relative risk reduction; resistance; salicyluric acid; thienopyridines; thromboxane; thromboxane A2

Document Type: Research Article

Publication date: 2010-12-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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