Aspirin resistance: causes, clinical significance, correction

Abstract

Aspirin is the most frequently prescribed antiplatelet agent today. It exerts its antiplatelet effect by irreversible inactivation of the platelet cyclooxygenase-1, resulting in an irreversible inhibition of thromboxane-A2 formation. The clinical benefit of antiplatelet therapy with acetylsalicylic acid (ASA) in high risk patients has been convincingly demonstrated through the results of multiple placebo-controlled trials. Nevertheless, a large number of patients treated with aspirin suffers an adverse cardiovascular event. This observation led to the concept of ”aspirin resistance“. The mechanisms of aspirin resistance remain to be determined, although different theories are being discussed. Several tests are used to assess resistance to ASA in vitro. Depending on which assay is used and which population is tested, the prevalence of aspirin resistance varies between 5% and 60%. So far, it was not possible to define a clear gold standard for detecting aspirin resistance, which considers both, biochemical data and clinical events, and correlates them in a reproducible way. The clinical implications of aspirin resistance are well-documented through a lot of studies, which conclude that resistance to aspirin in vitro is associated with a significant increased risk for adverse cardiovascular events in cardiovascular patients. Insufficient or excessive antiplatelet effect of acetylsalicylacid may be due not only to changes in the synthesized cyclooxygenase-1, but also to changes in its amount. Literature data on the association of various polymorphic markers of candidate genes with the effectiveness of antiplatelet therapy of ASA are few and contradictory. Therefore, it is currently impossible to identify genetic predictors of the effectiveness of ASA as well as any antiplatelet agent. Continuation of research in this area in the future will predict the patient’s response to a drug and, therefore, individualize the approach to the choice and dosage of antiplatelet drugs, which will reduce the incidence of adverse reactions.