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Ticagrelor in the treatment of coronary artery disease patients

Udaya S Tantry, Eliano Pio Navarese, Jacek Kubica, Young-Hoon Jeong and Paul A Gurbel

Clopidogrel is a major P2Y12 receptor blocker administered in addition to aspirin to reduce the ischemic event occurrence in a wide range of patients with arterial diseases particularly in patients treated with percutaneous coronary intervention (PCI). However, pharmacodynamic studies have disputed the ‘one size fits all’ dosing of

clopidogrel therapy and highlighted its limitations such as delayed onset of action; wide response variability with a substantial percentage of patients exhibiting high on-treatment platelet reactivity, which has been linked to worsened post-PCI ischemic outcomes; and irreversible inhibition, which is a concern in patients needing urgent surgery. The recently approved third-generation thienopyridine, prasugrel is associated with a faster onset of action, greater platelet inhibition, with less response variability and reduced ischemic event occurrence, and stent thrombosis compared with clopidogrel therapy in patients with acute coronary artery syndrome undergoing PCI. However, greater life-threatening risks and fatal bleeding associated with prasugrel therapy are major concerns. Ticagrelor is a direct-acting, reversibly binding and noncompetitive P2Y12 receptor blocker that is associated with faster onset of action and greater inhibition. In the PLATO trial, ticagrelor therapy was associated with reduced ischemic event occurrence than clopidogrel in acute coronary artery syndrome patients. Lower mortality and similar coronary artery bypass graft-related bleeding compared to clopidogrel are major advantages with ticagrelor therapy. Ticagrelor is recommended for patients with acute coronary syndrome treated with and without PCI. However, transient and nonsevere dyspnea and interaction with high aspirin dose are major concerns.