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  • Review Article
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Current concepts and novel targets for antiplatelet therapy

Nature Reviews Cardiology volume 20, pages 583–599 (2023)Cite this article

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Abstract

Platelets have a crucial role in haemostasis and atherothrombosis. Pharmacological control of platelet hyper-reactivity has become a cornerstone in the prevention of thrombo-ischaemic complications in atherosclerotic diseases. Current antiplatelet therapies substantially improve clinical outcomes in patients with coronary artery disease, but at the cost of increased risk of bleeding. Beyond their role in thrombosis, platelets are known to regulate inflammatory (thrombo-inflammatory) and microcirculatory pathways. Therefore, controlling platelet hyper-reactivity might have implications for both tissue inflammation (myocardial ischaemia) and vascular inflammation (vulnerable plaque formation) to prevent atherosclerosis. In this Review, we summarize the pathophysiological role of platelets in acute myocardial ischaemia, vascular inflammation and atherosclerotic progression. Furthermore, we highlight current clinical concepts of antiplatelet therapy that have contributed to improving patient care and have facilitated more individualized therapy. Finally, we discuss novel therapeutic targets and compounds for antiplatelet therapy that are currently in preclinical development, some of which have a more favourable safety profile than currently approved drugs with regard to bleeding risk. These novel antiplatelet targets might offer new strategies to treat cardiovascular disease.

Key points

  • Antiplatelet therapy improves prognosis in patients with cardiovascular disease.

  • Bleeding is a major complication of antiplatelet therapy and is associated with an increased risk of death.

  • A personalized antithrombotic strategy that takes into account the individual’s risk of ischaemic and bleeding events has been developed.

  • Novel targets have been identified and new drugs developed to suppress platelet-dependent thrombosis with fewer effects on haemostasis than conventional antiplatelet therapies, thus minimizing the risk of bleeding complications.

  • Targeting novel intracellular molecules might improve the efficacy and safety of antiplatelet therapy by supporting the microcirculation and functional recovery after myocardial ischaemia.

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Fig. 1: Platelets in atherothrombosis and myocardial ischaemia.
Fig. 2: Current antiplatelet concepts for the treatment of cardiovascular diseases.
Fig. 3: Novel antiplatelet drugs targeting surface receptors.
Fig. 4: Novel intracellular antiplatelet targets.

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Acknowledgements

The authors thank T. Castor (Eberhard Karls University of Tübingen, Germany) for help in the preparation of this article and M.-C. Manke (Eberhard Karls University of Tübingen, Germany) for help in preparing Fig. 4 for initial submission.

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  1. Department of Cardiology and Angiology, Eberhard Karls University of Tübingen, Tübingen, Germany

    Meinrad Gawaz, Tobias Geisler & Oliver Borst

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M.G. discussed the content of the Review. All authors contributed to researching data for the article, and writing, reviewing and editing the manuscript before submission.

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M.G. is the co-inventor of Revacept and is a co-founder of the biotechnology company AdvanceCor. The other authors declare no competing interests.

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Gawaz, M., Geisler, T. & Borst, O. Current concepts and novel targets for antiplatelet therapy. Nat Rev Cardiol 20, 583–599 (2023). https://doi.org/10.1038/s41569-023-00854-6

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