Elinogrel potassium: Receptor antagonist antiplatelet therapy

(Chemical Equation Presented) The pharmacological management of cardiovascular disease patients with antiplatelet therapy has undergone dramatic changes in recent years with the development of new and more potent P2Y 12 receptor antagonists. These agents have been developed to address the limitations of the most widely used P2Y12 receptor antagonist, clopidogrel. Among the limitations of clopidogrel addressed are response variability and resistance. The latter has been linked to ischemic event occurrence and stent thrombosis in patients treated with percutaneous intervention (PCI). The irreversible effect of clopidogrel is problematic in patients needing urgent surgery. Treatment with the recently approved third-generation thienopyridine prasugrel was associated with less ischemic event occurrence and stent thrombosis compared to clopidogrel therapy in patients with acute coronary artery syndrome (ACS) undergoing PCI. However, greater bleeding, including life-threatening and fatal bleeding, was observed in the prasugrel-treated patients. Ticagrelor is a member of a new class of P2Y12 inhibitors, the cyclopentyl-triazolo-pyrimidines (CPTP), the first direct-acting, reversiblybinding, noncompetitive P2Y12 receptor antagonist. Ticagrelor therapy resulted in less ischemic event occurrence than clopidogrel in ACS patients. An important potential advantage of ticagrelor is lower mortality and less coronary artery bypass graft-related bleeding than clopidogrel. However, ticagrelor therapy was associated with dyspnea in both phase II and III clinical trials. Cangrelor, an adenosine triphosphate (ATP) analogue, is a parenteral, direct, competitive and reversible P2Y12 inhibitor associated with rapid onset and offset of platelet inhibition (within minutes). However, in phase III trials cangrelor was not superior to placebo in reducing ischemic events in patients undergoing PCI who were treated with clopidogrel alone. Elinogrel (PRT-060128) is a novel, direct-acting, competitive and reversible P2Y12 receptor antagonist. Elinogrel is a first-in-class sulfonylurea that may be administered intravenously or orally. The latter route of administration may facilitate the transition from immediate to long-term therapy. Results from the INNOVATE-PCI (phase II) trial regarding the safety and antiplatelet efficacy of elinogrel compared to clopidogrel will be published soon. Copyright © 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

Duke Scholars

Author Paul Alfred Gurbel Medicine, Clinical Pharmacology