Restoring Platelet Function in Patients on P2Y 12 Receptor Inhibitor Treatment

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the current mainstay of pharmacological treatment in both patients with stable coronary artery disease and acute coronary syndrome managed invasively by percutaneous coronary intervention (PCI).1 The primary goal of DAPT is to reduce the risk of ischemic events including (re)-infarction and stent thrombosis. Contrary, this well-recognized ischemic benefit of DAPT is cut down by an increased on-treatment bleeding risk including major and fatal bleeding in both a nonoperative and operative setting like coronary artery bypass grafting (CABG).2,3 Bleeding risks differ for the currently available oral P2Y12 receptor inhibitors. On the basis of the results of large-scale clinical trials and the clinical experience in recent years, we considered that the risk of bleeding to be modest for the second-generation thienopyridine clopidogrel, whereas more potent platelet inhibition, such as it is delivered by the third-generation thienopyridine prasugrel or the cyclo-pentyl-triazolo-pyrimidine ticagrelor, comes along with a substantially higher risk of bleeding.2–4 Immediate and sustained restoration of platelet function in patients on DAPT may become mandatory in a nonoperative setting with acute bleeding (eg, intracranial bleeding) or during cardiac and noncardiac surgery. From a pharmacological point of view, the ability to restore platelet function may differ for the irreversibly acting P2Y12 receptor inhibitors clopidogrel and prasugrel when compared with the direct-acting reversibly binding antiplatelet agent ticagrelor. This is because of the circumstance that active metabolites of both clopidogrel and prasugrel exhibit a short plasma half-life and their binding to the P2Y12 receptor is …