High residual platelet reactivity on clopidogrel: its significance and therapeutic challenges overcoming clopidogrel resistance.

Over the last decade, dual antiplatelet therapy has been the mainstay of the management of Acute Coronary Syndrome, with clopidogrel therapy providing clear benefits over aspirin monotherapy and becoming the agent of choice for the prevention of stent thrombosis. While newer antiplatelet agents have now become available, clopidogrel is still widely used due to its low cost and efficacy. However, many patients still experience recurrent ischemic events. A poor response of the platelets to clopidogrel, called High Residual Platelet Reactivity (HRPR), has been incriminated to account for this dilemma. Despite the absence of a universal definition of HRPR or the gold standard test to quantify it, persistent high platelet reactivity has consistently been associated with recurrence of ischemic events. Clopidogrel metabolism is highly variable, and genetics, comorbidities and drug interactions can affect it. In this article we review all definitions of HRPR, explore the available tests to quantify it, the clinical outcomes associated with it, as well as strategies that have shown success in overcoming it.