Ticagrelor for the treatment of arterial thrombosis.
IMPORTANCE OF THE FIELD: High platelet reactivity has been linked to recurrent ischemic events in patients treated with conventional dual antiplatelet therapy, in patients with arterial diseases and particularly in patients treated with coronary artery stenting. The limitations of clopidogrel have served as a major rationale for the development of new P2Y(12) blockers that have superior pharmacodynamic profiles uninfluenced by concomitant therapies or specific genotypes. Ticagrelor is the first direct-acting reversibly binding oral P2Y(12) receptor antagonist. Extensive Phase II investigations have addressed the pharmacokinetic, pharmacodynamic and safety-related properties of ticagrelor compared with clopidogrel. The recently completed PLATO trial demonstrated promise for ticagrelor as a major treatment strategy for a wide spectrum of patients with acute coronary syndromes. Ticagrelor is now being reviewed by the FDA as a P2Y(12) receptor blocker to treat patients with coronary artery disease and, once accepted, will be in widespread use as an antiplatelet agent. Thus, it is both appropriate and timely to review available data and provide a comprehensive review of ticagrelor. AREAS COVERED IN THIS REVIEW: We discuss the rationale for the development of ticagrelor, a reversible and potent P2Y(12) receptor blocker. The data regarding ticagrelor based on preclinical and clinical studies are examined. We researched articles about 'AZD6140' and 'ticagrelor' in PubMed from 2006 to 2010 and also reviewed data presented at recent cardiology meetings. WHAT THE READER WILL GAIN: This is an updated and comprehensive review of ticagrelor. The advantages and disadvantages of ticagrelor and available P2Y(12) receptor blockers such as clopidogrel and prasugrel are discussed, thus providing a clear picture to readers. TAKE HOME MESSAGE: Ticagrelor has an important role as an antiplatelet agent in the settings of acute coronary syndrome and percutaneous coronary intervention and once accepted will be in widespread use.
Gurbel, PA; Kereiakes, DJ; Tantry, US
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