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Therapeutic strategies for thrombosis: new targets and approaches

Abstract

Antiplatelet agents and anticoagulants are a mainstay for the prevention and treatment of thrombosis. However, despite advances in antithrombotic therapy, a fundamental challenge is the side effect of bleeding. Improved understanding of the mechanisms of haemostasis and thrombosis has revealed new targets for attenuating thrombosis with the potential for less bleeding, including glycoprotein VI on platelets and factor XIa of the coagulation system. The efficacy and safety of new agents are currently being evaluated in phase III trials. This Review provides an overview of haemostasis and thrombosis, details the current landscape of antithrombotic agents, addresses challenges with preventing thromboembolic events in patients at high risk and describes the emerging therapeutic strategies that may break the inexorable link between antithrombotic therapy and bleeding risk.

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Fig. 1: Formation of an occlusive arterial thrombosis.
Fig. 2: Targets of current antithrombotic drugs.
Fig. 3: Targets of antiplatelet agents in development.
Fig. 4: Targets of anticoagulant agents in development.

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Acknowledgements

The authors would like to thank Cihan Ay, Jonathan Erlich, Steven Grover, Raj Kasthuri, Carolyn Mackman and Dougald Monroe III for helpful comments and Yohei Hisada for help with preparing the manuscript.

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Correspondence to Nigel Mackman.

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G.A.S. and W.B. have no competing interests. N.M. has a grant from Bayer and is a consultant for Bayer. J.I.W. is a consultant for Bristol-Myers Squibb, Pfizer, Daiichi Sankyo, Bayer, Janssen, Boehringer Ingelheim, IONIS Pharmaceuticals, Merck, Portola, Perosphere, Servier, Anthos and Tetherex.

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Glossary

Cardiovascular disease

Disorders of the heart and blood vessels.

Platelets

Small enucleate cells in the blood involved in clotting.

Haemostasis

Arrest of bleeding after damage to a blood vessel.

Antisense oligonucleotides

(ASOs). Antisense oligonucleotides reduce protein expression by binding to mRNA and increasing its degradation.

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Mackman, N., Bergmeier, W., Stouffer, G.A. et al. Therapeutic strategies for thrombosis: new targets and approaches. Nat Rev Drug Discov 19, 333–352 (2020). https://doi.org/10.1038/s41573-020-0061-0

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