Laboratory detection of 'aspirin resistance': what test should we use (if any)?

Abstract

Listen

Translate article

Aspirin is widely used to decrease the risk of occlusive arterial events in patients at risk. It irreversibly inhibits the cyclooxygenase-1 (COX-1)-dependent synthesis of thromboxane A2 (TxA2), which is essential for the full aggregation response of platelets. In the last years, the issue of ‘aspirin resistance’ has been emphasized in the medical literature.1–4 Despite several studies published on this subject, its definition, diagnosis, prevalence, causes, and clinical consequences are still uncertain.1 The term ‘resistance’ to a drug should be used when a drug is unable to hit its pharmacological target, due to inability to reach it (as a consequence of reduced bioavailability, in vivo inactivation, negative interaction with other substances) or to alterations of the target.1 Based on this definition, the term ‘resistance’ to aspirin should be limited to situations in which aspirin is unable to inhibit COX-1-dependent TxA2 production (and, consequently, TxA2-dependent platelet functions). ### ‘Aspirin resistance’ vs. ‘treatment failure’ If the anti-thrombotic effects of aspirin are dependent on inhibition of COX-1, one would expect that patients in whom aspirin does not inhibit COX-1 do not benefit from the protection that this drug provides and are exposed to high risk of atherothrombotic events. However, it is incorrect to consider ‘resistant’ to aspirin all those patients who experience atherothrombotic events while on treatment. This phenomenon has been named ‘clinical resistance’, but it should be more properly termed ‘treatment failure’.1,2 It can be observed with any kind of treatment and is expected to be particularly frequent for drugs, like aspirin and all other anti-thrombotic agents, that are used to prevent multi-factorial diseases, such as those associated with vascular occlusion, independently of their efficacy to hit their pharmacological targets. ### ‘Aspirin resistance’ vs. ‘high on-treatment residual platelet reactivity’ In consideration of the importance of TxA2 pathway in platelet activation, one would expect that … Corresponding author. Tel: +39 (0) 250323095; fax: +39 (0) 250323095. E-mail address : marco.cattaneo{at}unimi.it