Aspirin resistance: Fact or fiction? A point of view

Abstract

Aspirin is a wonder drug that has been used for well over 100 years for its analgesic and antipyretic effects. For the past three decades, it has increasingly been used for the prevention of primary and secondary cardiovascular events. Lately, it has been suggested that a significant number of individuals taking aspirin have become resistant to this drug. The phenomenon of "aspirin resistance" is based on the observation of clinical events in some patients taking aspirin, and/or a diminished platelet aggregation inhibitory response to aspirin therapy. Unfortunately, laboratory assays used to monitor the efficacy of aspirin are far from accurate and the results are not reproducible. Furthermore, results of different platelet function tests are often not congruent. In addition, platelet aggregation studies show marked inter-individual and intra-individual variability. Patients with coronary heart disease take many drugs that interfere with the effect of aspirin on platelet aggregation. Besides inhibiting formation of thromboxane A(2) from arachidonic acid, aspirin has a host of platelet-independent effects that complement its platelet inhibitory effects. Laboratory assays designed to measure platelet function do not take into account these pleiotropic effects of aspirin. In our view, use of the term "aspirin resistance" based on inadequate knowledge of imperfect laboratory tests does a disservice to physicians and patients.

Keywords: Aspirin; Cardiovascular diseases; Drug resistance; Treatment outcome.

Figure 1

Pathways of platelet aggregation. Platelets can be activated in response to collagen, von Willebrand factor (vWF) and tissue factor when there is injury to the endothelial lining. A host of other stimuli, such as adenosine diphosphate (ADP), 5-hydroxytryptamine (5-HT), epinephrine and thromboxane A₂ (TXA₂), can initiate aggregation via specific receptors. The end-point is the rise in cytosolic Ca²⁺ which induces platelet activation/aggregation. Externalization of glycoprotein (Gp)IIb/IIIa receptors causes fibrin bands to bind to different platelets. Aspirin interferes with the conversion of arachidonic acid (AA) to TXA₂ and inhibits the rise in cytosolic Ca²⁺ and subsequent platelet aggregation.