Aspirin resistance: an evaluation of current evidence and measurement methods.
Aspirin resistance is a poorly characterized phenomenon, whereby certain patients do not benefit from the antithrombotic effect of aspirin. The frequency of aspirin resistance is unknown, but estimates range from 5-60%. The mechanism of aspirin resistance also is unknown; proposed mechanisms are poor patient compliance, poor aspirin absorption, increased isoprostane activity, platelet hypersensitivity to agonists, increased cyclooxygenase-2 activity, a cyclooxygenase-1 polymorphism, and the platelet alloantigen 2 polymorphism of platelet glycoprotein IIIa. Aspirin resistance appears to be dose related in some patients and therefore may be overcome with high doses. Evidence indicates that aspirin resistance is a dynamic state, with significant intrapatient variability in aspirin sensitivity with time. To date, a sensitive and specific assay of aspirin effect that reliably predicts treatment failure has not emerged. However, several commercially available products are being marketed for this purpose without convincing clinical data. Despite a wealth of literature on the topic, aspirin resistance remains an enigma. Further investigation is needed regarding strategies to identify and treat patients resistant to aspirin.
Martin
Christopher P
CP
Division of Pharmacotherapy, College of Pharmacy, University of Texas at Austin, Austin, Texas, USA.
Talbert
Robert L
RL
D016824:Antigens, Human Platelet / Q000235:genetics; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000502:physiology*; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics; D008565:Membrane Proteins; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests / Q000379:methods*; D011110:Polymorphism, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
D016824:Antigens, Human Platelet; D039661:Integrin beta3; D008565:Membrane Proteins; D010975:Platelet Aggregation Inhibitors; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin