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  • Review Article
  • Published:

Switching P2Y12-receptor inhibitors in patients with coronary artery disease

Nature Reviews Cardiology volume 13, pages 11–27 (2016)Cite this article

Subjects

Key Points

  • Dual antiplatelet therapy with aspirin and a P2Y12-receptor inhibitor is the cornerstone of treatment of patients with acute coronary syndromes and of those undergoing percutaneous coronary intervention

  • Although the novel P2Y12-receptor inhibitors prasugrel and ticagrelor have been associated with better net clinical outcomes than clopidogrel in patients with acute coronary syndromes, clopidogrel is still frequently used

  • Switching between P2Y12 inhibitors is common in clinical practice, which has been attributed to multiple factors, including individual risk of bleeding and ischaemic events, socioeconomic factors, and pharmacodynamics and/or genetics

  • Drug interactions have been described when switching between P2Y12-receptor inhibitors (oral and intravenous) with different receptor-binding properties, which raises concerns about the optimal switching strategies

  • Guideline recommendations on how to switch from clopidogrel to prasugrel or ticagrelor and vice versa, as well as between prasugrel and ticagrelor, and between intravenous and oral therapies, are lacking

  • Understanding the pharmacological properties of P2Y12-inhibiting therapies (competitive or noncompetitive) and the timing of disease presentation (acute or chronic) are important factors to define switching strategies

Abstract

Dual antiplatelet therapy—the combination of aspirin and a P2Y12-receptor inhibitor—is the cornerstone of treatment of patients with acute coronary syndromes (ACS) and of those undergoing percutaneous coronary intervention. Prasugrel and ticagrelor have more prompt, potent, and predictable antiplatelet effects than those of clopidogrel, and result in reduced ischaemic outcomes in patients with ACS, albeit at the expense of an increased risk of bleeding. However, clopidogrel is still very commonly used. Switching between oral P2Y12-inhibiting therapies occurs very frequently in clinical practice for a variety of reasons, which raises the question of which switching approaches are preferable. In 2015, cangrelor (an intravenous P2Y12-receptor inhibitor) was approved for clinical use, which adds to the conundrum of how to switch between intravenous and oral therapies. Differences in the pharmacology of P2Y12-receptor inhibitors, such as their binding sites (competitive or noncompetitive), half-life, and speed of onset and offset of action, are important factors that might lead to drug interactions when switching between agents. In this Review, we provide an overview of the literature on switching antiplatelet treatment strategies with P2Y12-receptor inhibitors, and discuss practical considerations for switching therapies in the acute and chronic phases of disease presentation.

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Figure 1: Metabolism and mechanism of action of P2Y12-receptor inhibitors.
Figure 2: Binding properties of P2Y12-receptor inhibitors.23
Figure 3: Pharmacodynamic profile of switching from clopidogrel to prasugrel therapy: the SWAP study.45
Figure 4: Pharmacodynamic profile of switching from clopidogrel to prasugrel therapy: the TRIPLET study.47
Figure 5: Biological hypothesis for P2Y12-receptor occupancy after administration of a LD of prasugrel, with or without previous exposure to clopidogrel.
Figure 6: Pharmacodynamic profile of switching between clopidogrel and ticagrelor therapy: results from the RESPOND study.58
Figure 7: Pharmacodynamics profile of switching therapy from ticagrelor to prasugrel: results from the SWAP-2 study.82
Figure 8: Practical recommendations for switching between oral and intravenous antiplatelet agents.

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  1. University of Florida College of Medicine–Jacksonville, 655 West 8th Street, Jacksonville, 32209, FL, USA

    Fabiana Rollini, Francesco Franchi & Dominick J. Angiolillo

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All the authors researched data for the article, substantially contributed to discussion of content, and reviewed and edited the manuscript before submission. F.R. and D.J.A. wrote the manuscript.

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Correspondence to Dominick J. Angiolillo.

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Competing interests

D.J.A. has received payment as an individual for consulting fees or honoraria from Abbott Vascular, AstraZeneca, Daiichi-Sankyo, Eli Lilly, Merck, PLx Pharma, Sanofi, and The Medicines Company; and for participation in review activities from CeloNova, Johnson & Johnson, and St. Jude Medical. Institutional payments for grants have been received from AstraZeneca, CSL Behring, Daiichi-Sankyo, Eli Lilly, Gilead, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis, Osprey Medical, and The Medicines Company. The other authors declare no competing interests.

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Rollini, F., Franchi, F. & Angiolillo, D. Switching P2Y12-receptor inhibitors in patients with coronary artery disease. Nat Rev Cardiol 13, 11–27 (2016). https://doi.org/10.1038/nrcardio.2015.113

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