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Dual antiplatelet therapy in cardiovascular disease: does aspirin increase clinical risk in the presence of potent P2Y12 receptor antagonists?
  1. Timothy D Warner1,
  2. Paul C J Armstrong2,
  3. Nicholas P Curzen3,
  4. Jane A Mitchell4
  1. 1The William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, UK
  2. 2Atherothrombosis and Vascular Biology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
  3. 3Wessex Cardiothoracic Unit, Southampton University Hospital, Southampton, UK
  4. 4Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College School of Medicine, London, UK
  1. Correspondence to Professor Tim Warner, The William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK; t.d.warner{at}


Aspirin is now widely accepted as the first-line antithrombotic platelet therapy for at-risk individuals. During the last decade or so it has also become established that co-administering antagonists of the ADP receptor P2Y12 with aspirin further reduces the risk of acute thrombotic events. By the nature of its evolution, this therapeutic approach assumes that P2Y12 receptor antagonists will be added to aspirin, and this therefore dominates the design of clinical trials. This strategy has resulted in the generation of a large body of clinical evidence showing the benefit of aspirin plus P2Y12 receptor antagonists, largely from studies with clopidogrel and more recently from those with prasugrel and ticagrelor, but with obvious limitations in terms of residual ischaemic event rates and bleeding complications. It is our hypothesis, however, that when administered in the presence of potent P2Y12 receptor antagonists, aspirin could actually increase total cardiovascular risk, although this has never been tested in large outcome studies. Clearly, this potentially negative interaction could be of relevance to millions of patients.

  • Platelet activation
  • platelets
  • acute coronary syndrome
  • antiplatelet treatment

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  • Funding TDW has received research grant support and consultancy fees from AstraZeneca. NPC has received research grants and/or consultancy fees from Eli Lilly, AstraZeneca, Boston Scientific, Pfizer, Medtronic, Abbott Vascular and Cordis.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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