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ADP Receptor Antagonism

What’s in the Pipeline?

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Abstract

ADP is one of the most important mediators of both physiologic hemostasis and thrombosis. Development and utilization of agents that block ADP receptors on the platelet membrane, namely thienopyridines, has represented a major advancement for treatment of patients undergoing percutaneous coronary interventions and those with acute coronary syndromes. Currently, clopidogrel, a second-generation thienopyridine that inhibits the ADP P2Y12 receptor, represents the treatment of choice, in addition to aspirin, for the prevention of stent thrombosis. Further, long-term adjunctive use of this ADP P2Y12 receptor antagonist is also associated with improved clinical outcomes in high-risk patients, and represents the standard of care for these patients. Despite the unambiguous clinical benefit associated with clopidogrel, accumulating experience with this drug has also led to identification of some of its drawbacks, which are related to inadequate platelet inhibition with standard dosage regimens as well as to its irreversible antiplatelet effects. This has led to the questioning of currently recommended clopidogrel dosage regimens as well as to the development of novel and more potent ADP P2Y12 receptor antagonists, some of which are also reversible agents. Numerous studies are currently ongoing with the objective of demonstrating how more potent platelet inhibition using higher loading and maintenance dose regimens of clopidogrel or novel ADP P2Y12 receptor antagonists — such as prasugrel, ticagrelor (AZD 6140) and cangrelor — will affect clinical outcomes. This article reviews the current knowledge of platelet ADP P2Y12 receptor antagonism and the projected developments in this field.

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Acknowledgments

The author is a consultant for Bristol Myers Squibb, Daiichi Sankyo, Eli-Lilly, and Sanofi-Aventis and has received honoraria from Bristol Myers Squibb and Sanofi-Aventis. No sources of funding were used to assist in the preparation of this review.

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  1. Division of Cardiology, University of Florida, Shands, 655 West 8th Street, Jacksonville, Florida, 32209, USA

    Dominick J. Angiolillo

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Angiolillo, D.J. ADP Receptor Antagonism. Am J Cardiovasc Drugs 7, 423–432 (2007). https://doi.org/10.2165/00129784-200707060-00005

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