Antiplatelet function variability in clopidogrel-treated patients: need for new antiplatelet agents

Antiplatelet therapy is obligatory in patients with coronary artery disease (CAD) both in acute coronary syndromes (ACS) and in secondary prevention. Aspirin in combination with clopidogrel has been recommended as the main therapeutic regimen for many years. However, the high inter-individual variability of platelet aggregation seen with clopidogrel, caused by the underlying disease (more pronounced in diabetic patients and patients with ACS), drug interactions as well as by genetic variants leading to a reduced formation of the active metabolite of the prodrug clopidogrel, has confronted clinical practice with increasing numbers of adverse clinical events in patients following an ACS. Therefore, new antiplatelet agents have been investigated showing a more favorable efficacy/safety profile. Prasugrel as well as ticagrelor are meanwhile part of the recently published revascularization guidelines of the European Society of Cardiology based on their favorable results with respect to reducing a combined ischemic efficacy endpoint in patients with ACS in the TRITON-TIMI-38 (prasugrel) and PLATO (ticagrelor) trials. Different to clopidogrel, their effects are independent of genetic variants and also drug interactions seem neglectable. This article discusses the reasons for antiplatelet function variability of clopidogrel and presents clinical data of the new ADP-receptor inhibitors by reviewing the recently published trials and prespecified post hoc analyses of these trials as well as the potential use of the new antiplatelet agents in the near future.