BRAIN and NERVE Shinkei Kenkyu no Shinpo Volume 60, Issue 11 (November 2008)

Aspirin Resistance Shigeki Miyata 1 , Toshiyuki Miyata 2 , Akiko Kada 3 , Kazuyuki Nagatsuka 4 1Division of Transfusion Medicine,National Cardiovascular Center 2Research Institute,National Cardiovascular Center 3Department of Clinical Research and Development,National Cardiovascular Center 4Cerebrovascular Division,Department of Internal Medicine,National Cardiovascular Center Keyword: antiplatelet therapy , aspirin resistance , cyclooxygenase-1 , laboratory assay , cardiovascular events pp.1357-1364
Published Date 2008/11/1
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 Aspirin inhibits platelet activation through the permanent inactivation of the cyclooxygenase (COX) activity of prostaglandin H synthase-1 (referred to as COX-1),and consequently inhibits the biosynthesis of thromboxane A2 (TXA2),a platelet agonist. Recent meta-analysis has revealed that long-term aspirin administration has clear benefits for the secondary prevention of cardiovascular diseases with an odds reduction of 23% and an absolute risk reduction of 3.1% over 2 years. However,this indicates that not all individuals respond equally to aspirin therapy and cardiovascular events may occur during aspirin therapy,this is often denoted as "clinical aspirin resistance". Several reports have,indeed,suggested that the effect of aspirin administration varies considerably among the patients at high risk for cardiovascular events. Approximately one forth of the patients showed persistent platelet reactivity in vitro despite the use of aspirin (denoted "laboratory aspirin resistance"),this was determined by laboratory tests including the test for arachidonic acid-induced platelet aggregation and the assays using point-of-care devices. Recent clinical studies have proposed that resistance to aspirin (laboratory aspirin resistance) can relate to the cardiovascular outcomes in patients treated with aspirin (clinical aspirin resistance). A systematic review and meta-analysis on aspirin resistance have indicated that patients who are resistant to aspirin are at a greater risk (odds ratio: 3.85) of clinically important cardiovascular morbidity than patients who are sensitive to aspirin. However,many issues are yet to be resolved in order to apply the concept of "aspirin resistance" to actual clinical practice. The relevance of the various ex vivo functional indexes of platelet capacity to in vivo platelet activation and the precise mechanisms underlying aspirin resistance are still largely unknown. To assess what kind of laboratory assays is the best predictor for cardiovascular events and the risk factors of aspirin resistance,including non-compliance,concurrent intake of other drugs such as nonsteroid anti-inflammatory drugs,and polymorphism of COX-1,we have conducted a multicenter,prospective cohort study (ProGEAR study). We hope that these results will contribute to an individualized antiplatelet therapy through the identification of aspirin nonresponders as a high-risk group for cardiovascular events.

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BRAIN and NERVE-神経研究の進歩
60巻11号 (2008年11月)
電子版ISSN 1344-8129 印刷版ISSN 1881-6096 医学書院