Aspirin is integral to the
secondary prevention of
cardiovascular disease and acts to impair the development of platelet-mediated atherothromboembolic events by irreversible inhibition of platelet
cyclooxygenase-1 (COX-1). Inhibition of this
enzyme prevents the synthesis of the potent pro-aggregatory
prostanoid thromboxane A2. A large number of patients continue to experience atherothromboembolic events despite
aspirin therapy, so-called '
aspirin treatment failure', and this is multifactorial in aetiology. Approximately 10% however do not respond appropriately to
aspirin in a phenomenon known as '
aspirin resistance', which is defined by various laboratory techniques. In this review we discuss the reasons for
aspirin resistance in a systematic manner, starting from prescription of the
drug and ending at the level of the platelet. Poor medication adherence has been shown to be a cause of apparent
aspirin resistance, and may in fact be the largest contributory factor. Also important is high platelet turnover due to underlying inflammatory processes, such as
atherosclerosis and its complications, leading to faster regeneration of platelets, and hence of COX-1, at a rate that diminishes the efficacy of once daily dosing. Recent developments include the identification of
platelet glycoprotein IIIa as a potential
biomarker (as well as possible underlying mechanism) for
aspirin resistance and the discovery of an
anion efflux pump that expels intracellular
aspirin from platelets. The absolute as well as relative contributions of such factors to the phenomenon of
aspirin resistance are the subject of continuing research.