Abstract:Many patients suffer thrombotic events such as myocardial infarction, stroke and peripheral embolism despite therapy with recommended doses of all currently approved antiplatelet agents. Researchers have suggested that a subset of patients may be resistant to the antiplatelet effects of aspirin, and have developed substantial evidence to support this theory. The thienopyridines ticlopidine and clopidogrel and the glycoprotein IIb/IIIa inhibitors also exhibit substantial interpatient variability in the level of… Show more
“…Increasing the dosage of clopidogrel might be expected to overcome poor clinical response. However, this is not uniformly supported by results of clinical trials indicating that targeting an independent pathway may offer a more effective approach than attempting to overload an ineffective system [43].…”
Section: Poor Responsiveness To Clopidogrelmentioning
Dual antiplatelet therapy with aspirin and clopidogrel is routinely used to prevent thrombotic events in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI) in Japan. However, these agents have various limitations and some patients will experience further cardiovascular events. The purpose of this article is to review the antiplatelet agents currently used in patients undergoing PCI in Japan, to discuss the issues and limitations associated with these antiplatelet agents, and to characterize new antiplatelet agents currently under investigation in Japan. Particular emphasis is placed on the novel thienopyridine prasugrel, and the potential this drug has for overcoming the issues associated with other antiplatelet agents.
“…Increasing the dosage of clopidogrel might be expected to overcome poor clinical response. However, this is not uniformly supported by results of clinical trials indicating that targeting an independent pathway may offer a more effective approach than attempting to overload an ineffective system [43].…”
Section: Poor Responsiveness To Clopidogrelmentioning
Dual antiplatelet therapy with aspirin and clopidogrel is routinely used to prevent thrombotic events in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI) in Japan. However, these agents have various limitations and some patients will experience further cardiovascular events. The purpose of this article is to review the antiplatelet agents currently used in patients undergoing PCI in Japan, to discuss the issues and limitations associated with these antiplatelet agents, and to characterize new antiplatelet agents currently under investigation in Japan. Particular emphasis is placed on the novel thienopyridine prasugrel, and the potential this drug has for overcoming the issues associated with other antiplatelet agents.
“…This degree of receptor occupancy is associated with a median ADP-induced platelet aggregation response of < 10 % of baseline [81 -83]. During the course of the infusion, the extent of inhibition in most patients declines gradually and the consistency of inhibition becomes less uniform, perhaps due to the emergence of the platelet a granule storage pool of receptors [84,85]. Nevertheless, at the completion of the 12-h infusion, most patients continue to have > 80 % receptor occupancy, and the median platelet aggregation is ~20 % of baseline [81 -83, 86].…”
The central role played by the alphaIIb beta3 receptor in platelet aggregation, and hence in platelet thrombosis, has led to the development of a number of parenteral and oral glycoprotein (GP) IIb/IIIa inhibitors for use in cardiovascular disease states, such as acute coronary syndromes and stroke. The predominant effect of these agents is to inhibit platelet aggregation, although studies of alphaIIb beta3 receptor function and various GP IIb/IIIa inhibitors have demonstrated the potential for these agents to produce effects on other aspects of platelet function, in addition to non-platelet effects. Overall, clinical studies have demonstrated an impressive beneficial effect for parenteral agents in reducing ischemic complications following percutaneous intervention, and a more modest beneficial effect in the treatment of patients with acute coronary syndromes. Trials with oral GP IIb/IIIa inhibitors in similar patient populations have demonstrated toxicity, manifested by an increased mortality in treated patients. Increased understanding of molecular aspects of both alphaIIb beta3 receptor function and the effects of GP IIb/IIIa inhibition may help explain some of the inconsistency in recently reported clinical studies with parenteral agents, and the frank toxicity of oral agents. Such studies may also hold the key to the development of newer agents with enhanced therapeutic benefit.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.