New Directions in Antiplatelet Therapy

Abstract

A therosclerosis is a chronic inflammatory process that is known to be the underlying cause of coronary artery disease (CAD). 1 In addition to being the first step of primary hemostasis, platelets play a pivotal role in the thrombotic process that follows rupture, fissure, or erosion of an atherosclerotic plaque. 2 Because atherothrombotic events are essentially platelet-driven processes, this underscores the importance of antiplatelet agents, which represent the cornerstone of treatment, particularly in the settings of patients with acute coronary syndromes (ACS) and undergoing percutaneous coronary intervention (PCI).Currently, there are 3 different classes of antiplatelet drugs that are approved for clinical use and recommended per guidelines for the treatment and prevention of ischemic events in the settings of ACS and PCI: (1) cycloxigenase-1 (COX-1) inhibitor: aspirin, (2) adenosine diphosphate (ADP) P2Y 12 receptor antagonists: ticlopidine, clopidogrel, prasugrel, and ticagrelor, and (3) glycoprotein IIb/IIIa inhibitors (GPI): abciximab, eptifibatide, and tirofiban. 3-6 GPIs currently are available only for parenteral administration, and therefore their use is limited only to the acute phase of treatment of ACS patients undergoing PCI. Oral antiplatelet agents, namely aspirin and P2Y 12 receptor inhibitors, are recommended for prevention of ischemic events in both the acute and long-term phases of treatment. For over a decade, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been considered the standard of care in the setting of ACS and PCI. However, a considerable number of adverse ischemic events continue to occur with this DAPT regimen, which has led to the development of newer and more potent antiplatelet agents. The objective of the present manuscript is to provide an overview on the most recent advances of currently approved antiplatelet agents in the setting of ACS and PCI, as well as on emerging agents that are in clinical development (Figure 1). Other antiplatelet drugs that are available for clinical use, such as pentoxifylline, cilostazol, and dypirimidamole, but do not have an approved indication for patients with ACS or undergoing PCI, as well as advances in anticoagulant therapy, will not be discussed.

Stimulation of nitric oxide production contributes to the antiplatelet and antithrombotic effect of new peptide pENW (pGlu-Asn-Trp)

“…The activation and aggregation of platelets play an essential role in the development of vascular occlusive thrombi and increased cardiovascular risks in diabetes [2][3][4]. Antiplatelet therapy has emerged as a primary target in the treatment of thrombotic disorders such as acute coronary syndromes [5,6]. However, with currently used antiplatelet drugs considerable adverse events -severe bleeding related to unexpected potency, adverse ischemia caused by poor antiplatelet activity -continue to occur.…”

Novel antiplatelet agents in acute coronary syndrome

“…52 Although the active metabolites of prasugrel and clopidogrel have the same in vitro affinity for the P2Y 12 -receptor, the metabolic conversion of prasugrel is more efficient, and results in higher in vivo availability. 53 These pharmacological properties of prasugrel translate into a faster onset of action, a more-potent antiplatelet effect, and lower interindividual response variability than with clopidogrel.…”

“…74 Ticagrelor Ticagrelor is an orally administered agent that is not a prodrug and so does not require metabolic activation. 52 This first-in-class cyclopentyltriazolopyrimidine directly and reversibly inhibits the platelet P2Y 12 -receptor through allosteric modulation (Figure 3; Table 1). 52 How ever, approximately 30-40% of the antiplatelet effects mediated by ticagrelor are attributed to an active metabolite (AR-C124910XX) generated by hepatic CYP3A4 and CYP3A5.…”

Simultaneous screening and analysis of antiplatelet aggregation active alkaloids from Rhizoma Corydalis

“…As an essential physiological role in homeostasis, there are many receptors and proteins on the surface of platelet (Ferreiro & Angiolillo 2012), suggesting that, as a biomaterial, platelet can also be used to bind and separate active compounds through the interaction between them. Several studies reported the discovery of potential active compounds through bio-specific extraction.…”