Dual antiplatelet therapy in cardiovascular disease: does aspirin increase clinical risk in the presence of potent P2Y12 receptor antagonists?
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 P2Y(12) with aspirin further reduces the risk of acute thrombotic events. By the nature of its evolution, this therapeutic approach assumes that P2Y(12) 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 P2Y(12) 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 P2Y(12) 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.
Warner
Timothy D
TD
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@qmul.ac.uk
Armstrong
Paul C J
PC
Curzen
Nicholas P
NP
Mitchell
Jane A
JA
D001241:Aspirin / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000517:prevention & control; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12
C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D001241:Aspirin