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Novel antiplatelet agents in acute coronary syndrome

Nature Reviews Cardiology volume 12, pages 30–47 (2015)Cite this article

Subjects

Key Points

  • Platelet adhesion, activation, and aggregation after plaque rupture or erosion are the major determinants of arterial thrombosis leading to acute coronary syndrome (ACS)

  • Antiplatelet therapy, which targets pathways of platelet activation and aggregation, is pivotal in both the acute treatment and long-term secondary prevention of ischaemic events in patients with ACS

  • Dual antiplatelet therapy with a combination of aspirin and either prasugrel or ticagrelor should be the treatment of choice in patients with ACS

  • Drug selection should be based on contraindications and the individual patient's characteristics; clopidogrel should be used when both prasugrel and ticagrelor are contraindicated or not available

  • Patients might continue to experience adverse events despite the use of prasugrel or ticagrelor

  • New intravenous P2Y purinoceptor 12 inhibitors and agents that target other platelet-activation pathways have been developed

Abstract

For more than 10 years, dual antiplatelet therapy with aspirin and clopidogrel has remained the cornerstone of treatment for patients with acute coronary syndrome (ACS). The novel oral P2Y purinoceptor 12 (P2Y12)-receptor inhibitors prasugrel and ticagrelor were approved by the FDA for clinical use in 2009 and 2011, respectively. These agents have a faster-acting, more-potent, and more-predictable antiplatelet effect than clopidogrel, which translates into improved clinical outcomes in patients with ACS, albeit at the expense of an increased risk of bleeding. However, some patients continue to experience adverse ischaemic events despite treatment with aspirin and a P2Y12-receptor antagonist, because platelets can remain activated via pathways not inhibited by these agents, such as the protease-activated receptor (PAR)-1 platelet activation pathway stimulated by thrombin. Emerging antiplatelet therapies that might address these limitations include intravenous P2Y12 antagonists, oral PAR-1 antagonists, and thromboxane-receptor inhibitors. In this Review, we provide an overview of these novel antiplatelet drugs, including newly approved agents and emerging compounds currently under clinical development, and also discuss evolving concepts and unmet needs related to antiplatelet therapy for the treatment of ACS.

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Figure 1: Mechanism of thrombus formation.
Figure 2: Platelet activation pathways targeted by current and novel antiplatelet agents.
Figure 3: Mechanisms of action of P2Y12 inhibitors.

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  1. Division of Cardiology, ACC Building 5th Floor, University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, 32209, FL, USA

    Francesco Franchi & Dominick J. Angiolillo

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F.F. and D.J.A. researched, discussed, wrote, reviewed, and edited the manuscript before submission.

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D.J.A. declares that he has received honoraria from Abbott Vascular, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Evolva, Merck, PLx Pharma, Sanofi-Aventis, and The Medicines Company; has participated in review activities for CeloNova BioSciences, Johnson & Johnson, St. Jude Medical, and Sunovion Pharmaceuticals; and has received institutional payment for grants from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Evolva, Gilead, GlaxoSmithKline, Otsuka, Sanofi-Aventis, and The Medicines Company. F.F. declares no competing interests.

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Franchi, F., Angiolillo, D. Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol 12, 30–47 (2015). https://doi.org/10.1038/nrcardio.2014.156

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