Novel antiplatelet agents in development: prasugrel, ticagrelor, and cangrelor and beyond.
Coronary artery disease, stroke, and peripheral vascular disease are known as "atherothrombotic" manifestations of atherosclerosis. These devastating conditions remain the major contributor of mortality and disability in a modern Western world, with estimated direct and indirect cost for 403.1 billion dollars in the United States alone. The application of current evidence-based therapy including the administration of low-dose aspirin and standard of care with clopidogrel proved to exhibit absolute mortality reduction in the randomized clinical trials International Study for Infarct Survival and Clopidogrel and Metoprolol in Myocardial Infarction Trial among patients after acute vascular events. However, these established antiplatelet medications have certain shortcomings including lack of efficacy in some patients, significant response variability, and potential "resistance." Therefore, intelligent development of novel oral antiplatelet agents is difficult to underestimate. In this review, we will focus on the developmental efforts with regard to the experimental agents such as adenosine diphosphate receptor blockers (prasugrel, ticagrelor, and cangrelor) and platelet glycoprotein VI adhesion antagonist [ProCorde GmbH 15 (PR-15)].
Shalito
Inna
I
HeartDrug Research Laboratories, Johns Hopkins University, Towson, MD 21204, USA.
Kopyleva
Olga
O
Serebruany
Victor
V
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D015195:Drug Design; D006801:Humans; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D000068799:Prasugrel Hydrochloride; D058919:Purinergic P2 Receptor Antagonists; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use; D000077486:Ticagrelor
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D058919:Purinergic P2 Receptor Antagonists; D013876:Thiophenes; C098341:platelet membrane glycoprotein VI; D000249:Adenosine Monophosphate; C117446:cangrelor; D000068799:Prasugrel Hydrochloride; D000077486:Ticagrelor; D000241:Adenosine