Poor response to antiplatelet drugs. An important issue in drug-eluting stents

Platelet aggregation activity is the cornerstone of the pathogenesis of atherothrombosis and plays a main role in the appearance of major adverse cardiac events (MACE). This aspect has become even more important nowadays due to the use of drug-eluting stents (DES), where a proper platelet inhibition is required. Dual antiplatelet therapy with aspirin and clopidogrel in patients undergoing percutaneous coronary intervention (PCI) has widely demonstrated its beneficial effect in reducing MACE compared with aspirin alone. These benefits had also been established in short and long term treatment in patients with coronary artery disease managed with a conservative strategy. However, despite dual antiplatelet therapy an important number of patients experience new MACE related to an incomplete platelet inhibition that can be caused by the interaction of different mechanisms, not fully known at the moment. Several clinical studies suggested the significant variability in individual patient response to antiplatelet drugs to be due to the use of different laboratory tests. Moreover, other studies associated the low responsiveness status with an increased risk of recurrent cardiovascular events. Notably, resistance or reduced response to antiplatelet therapy with aspirin and clopidogrel is a clinically relevant entity that needs to be taken into account in order to perform a proper and individualized treatment strategy. Recent antiplatelet drugs such as prasugrel and ticagrelor have appeared to be an attractive option for patients with resistance or low response to traditional therapy. In this article we review aspirin and clopidogrel resistance as a clinical entity, the different mechanisms that could be linked to treatment failure, its relation with special situations and future perspectives in this area.