P2Y12 antagonists as antiplatelet agents - Recent developments

Antiplatelet therapy is a crucial component of disease management for patients with acute coronary syndromes or chronic stable coronary disease, as well as individuals undergoing percutaneous coronary intervention with stent implantation. Antiplatelet therapy includes the administration of aspirin and clopidogrel, either alone or in combination, which act through the inhibition of thromboxane A(2) generation and blockade of the G(i)-coupled P2Y(12) purinergic receptor, respectively. Because of the selective expression and specific functions of P2Y(12), this receptor has become an important antiplatelet drug target. P2Y(12) antagonists can be broadly classified as either irreversible or reversible. Clopidogrel, an irreversible P2Y(12) antagonist, has a delayed onset of action and high inter-individual variability. Limitations of clopidogrel have necessitated the discovery of novel P2Y(12) antagonists with superior pharmacological profiles. This review summarizes recent studies on novel P2Y(12) antagonists and the clinical implications and limitations of these agents.