New antiplatelet drugs: beyond aspirin and clopidogrel

Abstract

Antiplatelet therapy remains a cornerstone of modern management of atherothrombotic vascular disease. For many years, aspirin has been the mainstay of initial antiplatelet drug management in coronary heart disease, while the need for inhibition of other platelet activation pathways has led to the development of various other antiplatelet drugs, such as clopidogrel. An improved understanding of the underlying mechanisms involved in thrombogenesis has paved the way for further development of newer antiplatelet drug therapies. Various clinical studies have probed the effectiveness and risk profile of the newer antiplatelet drugs, such as prasugrel, in comparison with currently available drugs. Some newer agents such as prasugrel are close to being approved for clinical use, whereas other agents such as cangrelor and AZD6140 are in phase 3 clinical trials. New drug classes, such as the thromboxane receptor antagonists (such as NCX-4016 and S18886), as well as platelet adhesion antagonists and thrombin receptor antagonists are similarly being evaluated for their efficacy and risk profile in phase I and II trials.

Glycoprotein Ibα inhibitor complex structure reveals a combined steric and allosteric mechanism of von Willebrand factor antagonism

“…Antiplatelet agents such as integrin ␣ IIb ␤ 3 (glycoprotein IIb/IIIa) inhibitors, aspirin, and clopidogrel have proven efficacy but cardiovascular disease remains an important cause of mortality that has prompted the search for novel drugs against platelet-dependent thrombosis. 13 Ligand mimetic peptide complex crystal structures for the platelet receptors integrin ␣ IIb ␤ 3 with RGD 14 and ␣ 2 ␤ 1 with a collagen peptide 15 have been described, and the former are currently in therapeutic use for treatment of thromboembolic disorders. Our data provide a new scaffold for designing antiplatelet agents targeting the GpIb␣-VWF-A1 interaction using small molecules or ␣-helical peptide derivatives of the OS1 sequence that are capable of occupying the GpIb␣ allosteric site defined in this complex structure.…”

Antithrombotic Drugs (Anticoagulants, Antiplatelets, and Thrombolytics)

“…Pharmacology, mechanisms of action, strategies of implementation, and uncertainties about antiplatelet drugs that are intended to prevent and/or reverse platelet aggregation in arterial thrombosis are summarized in several excellent books and reviews [116][117][118][119][120][121][122][123][124][125][126][127][128].…”

Pharmacological actions of miltirone in the modulation of platelet function

“…Although some new ADP receptor antagonists show a more rapid onset time and oral αIIbβ3 antagonists are getting some breakthrough, they are still troubled by bleeding and resistance. Thus it remains a pressing priority to find a safer and more effective anti-platelet agent [8,9].…”