title: New perspectives in antiplatelet therapy.
abstract: Platelet activation is a complex mechanism of response to vascular injury and atherothrombotic disease, leading to thrombus formation. A wide variety of surface receptors -integrins, leucine-rich family receptors, G protein coupled receptors, tyrosine kinase receptors- and intraplatelet molecules support and regulate platelet activation. They are potential targets of antiplatelet therapy for the prevention and treatment of arterial thrombosis. Despite the overall clinical benefit of established antiplatelet drugs targeting cyclooxigenase-1 (COX-1), glycoprotein integrin αIIbβ3, and the purinergic P2Y(12) receptor of adenosine diphosphate, a significant proportion of treated patients continue to experience recurrent ischaemic events. This may be in partly attributed to insufficient inhibition of platelet activation. In addition, it should not be underestimated that these drugs are not immune from bleeding complications. The substantial progress in understating the regulation of platelet activation has played a key role in the development of novel antiplatelet agents. Current examples of drug under development and evaluation include: novel P2Y(12) receptor inhibitors (prasugrel, ticagrelor, cangrelor, and elinogrel), thrombin receptor PAR-1 antagonists (vorapaxar, atopaxar), new integrin glycoprotein IIb/IIIa inhibitors, and inhibitors targeting the thromboxane receptor (TP), phosphodiesterases, the collagen receptor glycoprotein VI, and intraplatelet signalling molecules. This review summarizes the mechanisms of action and current clinical evaluation of these novel antiplatelet agents.
authors.affiliation: Department of Cardiology, Hospital Universitario Virgen de la Arrixaca, Ctra Madrid-Cartagena Murcia, 30120, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Tello-Montoliu
authors.forename: E
authors.initials: E
authors.lastname: Jover
authors.forename: J
authors.initials: J
authors.lastname: Rivera
authors.forename: M
authors.initials: M
authors.lastname: Valdés
authors.forename: D J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: F
authors.initials: F
authors.lastname: Marín
mesh_terms: D006801:Humans; D008954:Models, Biological; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D058919:Purinergic P2 Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D044463:Receptor, PAR-1 / Q000378:metabolism; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000378:metabolism; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control
chemical_list: D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D058919:Purinergic P2 Receptor Antagonists; D044463:Receptor, PAR-1; D017482:Receptors, Thromboxane