Document Detail

Mortality Benefit in PLATO Cannot Be Explained by Antiplatelet Properties of Ticagrelor.
MedLine Citation:
PMID:  21212672     Owner:  NLM     Status:  In-Data-Review    
The striking success of ticagrelor in PLATO when compared with recent important but far less impressive antiplatelet trials suggests the fundamental difference of ticagrelor from thienopyridines, such as ticlopidone, clopidogrel, and prasugrel. In fact, being a P2Y12 platelet receptor inhibitor, ticagrelor does not belong to the thienopyridines. The agent is a carbocyclic nucleoside, representing a 'first-in-class' cyclopentyl-triazolo-pyrimidine. The chemical structure of ticagrelor indicates that its primary mechanism of action may be via up-regulating plasma and intracellular adenosine content, especially considering the obvious similarity of their molecules. Since ticagrelor does not require hepatic metabolization, an adenosine-promoting mechanism of action is the most likely responsible pathway. Some of the delayed and growing mortality advantage of ticagrelor over clopidogrel cannot be explained by pure antiplatelet properties of the drug, but may be attributed to the off-target pleiothropic effects of the novel agent. An adenosine-mediated mechanism is most likely responsible for the fundamental difference of ticagrelor from established antiplatelet agents, and resulted in less heart failure deaths, and reduction of fatal arrhythmias. However, massive prevention of vascular death mismatched with conventional myocardial infarction rates, and reduction of sepsis-related mortality still lacks reasonable explanation, being under the scope of the regulatory agencies around the world. Future randomized trials of ticagrelor in acute heart failure, sudden death prevention, and treatment of atrial fibrillation are warranted, and may expand our understanding of the mechanism of action of pyrimidines in general, and ticagrelor in particular.
Victor L Serebruany
Publication Detail:
Type:  Editorial     Date:  2011-01-05
Journal Detail:
Title:  Cardiology     Volume:  117     ISSN:  1421-9751     ISO Abbreviation:  Cardiology     Publication Date:  2010  
Date Detail:
Created Date:  2011-01-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1266406     Medline TA:  Cardiology     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  231-3     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
HeartDrug™ Research Laboratories, Johns Hopkins University, Osler Medical Building, Towson, Md., USA.
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