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Education in Heart
Clinical pharmacology
New P2Y12 inhibitors
  1. Robert F Storey
  1. Correspondence to Professor Robert F Storey, Department of Cardiovascular Science, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK; r.f.storey{at}sheffield.ac.uk

https://doi.org/10.1136/hrt.2009.184242

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    The management and prevention of arterial thrombosis has been transformed by the recognition of the role of platelets in this process and the development of effective antiplatelet drugs. The limited role of thromboxane A2 in platelet activation explains why aspirin therapy, which effectively inhibits release of thromboxane A2 by platelets, is insufficient in high risk conditions such as acute coronary syndromes (ACS) or percutaneous coronary intervention (PCI). The platelet P2Y12 receptor, one of two adenosine diphosphate (ADP) receptors on platelets, plays a central and unique role in platelet activation through amplifying the effects of numerous platelet agonists (figure 1).1 Platelet activation leads not only to aggregation but also to the release of pro-thrombotic and pro-inflammatory granule contents as well as the formation of thrombin. Strong amplification of all these platelet responses by P2Y12 explains why this receptor plays such an important part in thrombosis and haemostasis and is a successful target for antiplatelet drugs.

    Figure 1

    Mechanisms of platelet activation and site of action of platelet inhibitors. Numerous platelet surface receptors initiate platelet activation leading to platelet aggregation, release of alpha and dense granule contents, and conversion of the platelet surface membrane to a catalytic surface for thrombin generation (‘platelet procoagulant activity’). Collagen binding to GPVI is an important stimulus for thromboxane A2 release. ADP released from dense granules binds to P2Y1 and P2Y12 receptors and P2Y12 acts as a powerful amplification system for platelet activation and all the functional responses associated with this. Platelet alpha granule contents support coagulation and, through multiple mechanisms, drive the inflammatory response associated with thrombosis. The sites of action of important antiplatelet drugs are shown. Adapted from Storey.1

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    Footnotes

    • Competing interests In compliance with EBAC/EACCME guidelines, all authors participating in Education in Heart have disclosed potential conflicts of interest that might cause a bias in the article. Professor Storey was an Executive Committee member and UK National Co-ordinating Investigator for the DISPERSE2 and PLATO studies and is an Executive Committee member and UK National Co-ordinating Investigator of the PEGASUS-TIMI 54 study and UK National Co-ordinating Investigator of the EPICOR, BRIDGE and ATLANTIC studies. He has received consultancy fees, honoraria and/or institutional research grants from AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, Novartis, Sanofi Aventis, Bristol Myers Squibb, GlaxoSmithKline, Eisai, Schering Plough, Merck, Teva, Dynabyte Accumetrics and Medscape and is Chair of the European Platelet Academy supported by unrestricted educational grants from Eli Lilly/Daiichi Sankyo and Accumetrics.

    • Provenance and peer review Commissioned; internally peer reviewed.