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  • Review Article
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Antiplatelet therapies for the treatment of cardiovascular disease

Nature Reviews Drug Discovery volume 9, pages 154–169 (2010)Cite this article

Subjects

Key Points

  • Antiplatelet therapy has been successful in reducing mortality and morbidity in acute myocardial infarction, which is the most common cause of death in the developed world.

  • Current antiplatelet therapies target key pathways of platelet activation, including thromboxane A2 synthesis (aspirin), ADP-mediated signalling (clopidogrel) and integrin αIIbβ3 (also known as GPIIb–IIIa) signalling.

  • Limitations of current therapies include weak inhibition of platelet function (for example, by aspirin), blockade of only one pathway of ADP-mediated signalling (for example, by clopidogrel), slow onset of action (for example, of clopidogrel), interpatient response variability with poor inhibition of platelet response in some patients (for example, to clopidogrel), inability to translate the success of intravenous integrin αIIbβ3 antagonist therapy into oral therapy, and the inability to completely separate a reduction in thrombotic events from an increase in bleeding events.

  • Recent advances in understanding the molecular basis of the role of platelets in cardiovascular thrombosis has enabled the development of new agents with the potential to further reduce mortality and morbidity, with the goal of better separating reduced thrombotic events from increased bleeding events.

  • Examples of these new agents include: ADP receptor antagonists with a more rapid onset of action, a more potent antiplatelet effect, and less patient hyporesponsiveness; integrin αIIbβ3 antagonists directed against new epitope targets; and agents directed against new platelet surface targets such as proteinase-activated receptor 1, glycoprotein VI, integrin α2β1, 5-hydroxytryptamine receptor 2A, and prostaglandin E2 receptor EP3 subtype.

Abstract

Antiplatelet therapy has been successful in reducing mortality and morbidity in acute myocardial infarction. Recent advances in understanding the molecular basis of the role of platelets in cardiovascular thrombosis have enabled the development of new agents with the potential to further reduce mortality and morbidity. This article reviews the role of platelets in haemostasis and cardiovascular thrombosis, and discusses the benefits and limitations of current and investigational antiplatelet agents in the treatment of cardiovascular disease.

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Figure 1: Platelet function and molecular targets of antiplatelet agents.

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  1. Center for Platelet Research Studies, Children's Hospital Boston, Karp 08213, 300 Longwood Avenue, Boston, 02115-5737, Massachusetts, USA

    Alan D. Michelson

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A.D.M. has been the principal investigator or co-investigator on research grants to the University of Massachusetts Medical School, Children's Hospital Boston, or both from Arena Pharmaceuticals, GLSynthesis, Lilly/Daiichi Sankyo and Sanofi–Aventis/Bristol–Myers Squibb. He has been a member of the Data Safety Monitoring Board of Clopidogrel to Lower Arterial Thrombotic Risk in Neonates and Infants Trial (CLARINET) (a clinical trial sponsored by Sanofi–Aventis/Bristol–Myers Squibb) and a consultant to Arena Pharmaceuticals and Lilly/Daiichi Sankyo.

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Glossary

Acute myocardial infarction

Popularly known as a heart attack, this is the death of heart tissue from lack of oxygen, which is usually caused by a clot (thrombosis) in an artery that supplies blood to the heart.

Thrombosis

The development of a blood clot in the circulatory system. Depending on the location of the clot, the resultant loss of circulation can lead to a heart attack (coronary thrombosis) or a stroke (cerebral thrombosis).

Haemostasis

The normal process of stopping bleeding.

Platelet aggregation

The process by which platelets adhere to one another, mediated by integrin αIIbβ3.

Cyclic flow reductions

Changes in blood flow over time that are dependent on the formation and dissolution of platelet aggregates.

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Michelson, A. Antiplatelet therapies for the treatment of cardiovascular disease. Nat Rev Drug Discov 9, 154–169 (2010). https://doi.org/10.1038/nrd2957

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