Simultaneous Platelet P2Y12 and P2Y1 ADP Receptor Blockade: Are Two Better Than One?

Abstract

Human platelets possess 3 purinergic receptors (P2Y12, P2Y1, and P2X1), which collectively orchestrate key steps leading to platelet activation and aggregation (Figure). Until now, the selective blockade of the platelet P2Y12 ADP receptor, combined with the inhibition of thromboxane production by aspirin, has remained the backbone of pharmacotherapy for patients presenting with acute coronary syndrome or undergoing percutaneous coronary intervention.1 Figure. The investigational modified diadenosine tetraphosphate (Ap4A) derivative, GLS-409, in the context of major classes of currently approved antiplatelet therapies and their respective pharmacologic targets. COX indicates cyclooxygenase; F, fibrinogen; GP, glycoprotein; PAR, protease-activated receptor; and T, thrombin. See accompanying article on page 501 Despite significant progress in the attenuation of excess platelet activity in these high-risk settings, percutaneous coronary intervention–related thrombotic complications, including stent thrombosis, and severe bleeding continue to be major sources of morbidity and mortality. Early after acute coronary syndrome, patients may …