Acetylsalicylic acid and clopidogrel hyporesponsiveness following acute coronary syndromes

Abstract

This review discusses the response variability to acetylsalicylic acid (ASA) and particularly to clopidogrel, and their relatio to adverse recurrent ischaemic events in patients with arterial diseases. The higher rate of ASA resistance reported in th literature may be mainly due to the cyclooxygenase-1 non-specific assays, non-compliance, and underdosing. Clopidogre response variability and non-responsiveness are established concepts. Moreover, high platelet reactivity (HPR) to adenosin diphosphate during clopidogrel therapy is now a known risk factor for recurrent ischaemic events in high-risk percutaneou coronary intervention/acute coronary syndrome patients. Variable active metabolite generation is the primary explanation fo clopidogrel response variability and non-responsivenes. Variable levels of active metabolite generation following clopidogre administration could be mainly explained by functional variability in hepatic cytochrome (CYP)P450 isoenzyme activity tha is influenced by drug–drug interactions and single nucleotide polymorphisms of specific genes encoding CYP450 isoen zymes. Treatment with more potent P2Y12 receptor blockers, such as prasugrel and ticagrelor are credible alternative strategie to overcome HPR during clopidogrel therapy.