Platelet thrombin receptor antagonism and atherothrombosis.

European Heart Journal
Dominick J AngiolilloShinya Goto

Abstract

Clinical manifestations of atherothrombotic disease, such as acute coronary syndromes, cerebrovascular events, and peripheral arterial disease, are major causes of mortality and morbidity worldwide. Platelet activation and aggregation are ultimately responsible for the progression and clinical presentations of atherothrombotic disease. The current standard of care, dual oral antiplatelet therapy with aspirin and the P2Y(12) adenosine diphosphate (ADP) receptor inhibitor clopidogrel, has been shown to improve outcomes in patients with atherothrombotic disease. However, aspirin and P2Y(12) inhibitors target the thromboxane A(2) and the ADP P2Y(12) platelet activation pathways and minimally affect other pathways, while agonists such as thrombin, considered to be the most potent platelet activator, continue to stimulate platelet activation and thrombosis. This may help explain why patients continue to experience recurrent ischaemic events despite receiving such therapy. Furthermore, aspirin and P2Y(12) receptor antagonists are associated with bleeding risk, as the pathways they inhibit are critical for haemostasis. The challenge remains to develop therapies that more effectively inhibit platelet activation without increasing bleedi...Continue Reading

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Methods Mentioned

BETA
nucleotide exchange

Clinical Trials Mentioned

NCT00526474
NCT00527943
NCT00312052
NCT00548587

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