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Porto, I. et al.

Italo Porto, Simona Giubilato, Giovanni Luigi De Maria, Luigi Marzio Biasucci, Filippo Crea,

Platelet P2Y12 receptor inhibition by thienopyridines: status and future.

Thienopyridines have a well-established role in the treatment of coronary artery disease, especially in the setting of acute coronary syndromes and percutaneous coronary interventions. Ticlopidine, the first FDA-approved thienopyridine, was shown to be effective in reducing coronary events in high risk patients, but the original enthusiasm was hampered by concerns about its serious bone marrow toxicity. Clopidogrel a second generation thienopyridine with lesser side effects, is not only at least as effective as ticlopidine, but in combination with a low dose of aspirin, has been demonstrated to reduce the risk of major cardiovascular events in acute coronary syndrome patients in large-scale, randomised trials. Recent studies have highlighted major flaws in clopidogrel pharmacokinetics due to its delayed onset of action, and much attention has been devoted to the phenomenon of clopidogrel 'resistance'. Among the novel, third generation thienopyridines, prasugrel as compared to clopidogrel has demonstrated lower inter-patient response variability and a reduced incidence of ischaemic events, but at an increased risk of major bleeding. Currently, several studies are continuing to test new direct P2Y12 receptor antagonists, such as cangrelor and AZD6140, characterised by a faster reversal of platelet inhibition.[1]

References

Platelet P2Y12 receptor inhibition by thienopyridines: status and future. Porto, I., Giubilato, S., De Maria, G.L., Biasucci, L.M., Crea, F. Expert. Opin. Investig. Drugs (2009) [Pubmed]

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