Mechanism of action and clinical development of ticagrelor, a novel platelet ADP P2Y12 receptor antagonist.
Inhibition of the platelet ADP P2Y(12) receptor has shown to be associated with a marked risk reduction of atherothrombotic events in high-risk settings, including patients with acute coronary syndromes and those undergoing percutaneous coronary interventions. Clinical and laboratory experiences have led to a better comprehension of the drawbacks of currently available P2Y(12) receptor antagonists, stimulating the development of novel agents. Ticagrelor (AZD6140) is the first drug of a new chemical class called cyclopentyltriazolopyrimidine, which is administered orally and has a reversible P2Y(12) receptor inhibitory effect. Preclinical and early-phase clinical studies have shown ticagrelor to be characterized by a rapid, greater and consistent antiplatelet effect with a favorable safety profile. Recent findings from large-scale Phase III trials showed ticagrelor to be more effective in preventing ischemic events in acute coronary syndrome patients without an increased risk of protocol-defined major bleeding, but with an increase in the rate of nonprocedure-related bleeding, compared with currently recommended treatment regimens. This article provides an overview of the pharmacologic properties and clinical development of ticagrelor.
University of Florida College of Medicine, Jacksonville, FL 32209, USA. dominick.angiolillo@jax.ufl.edu
Davide
D
Capodanno
Kodlipet
K
Dharmashankar
Dominick J
DJ
Angiolillo
D054058:Acute Coronary Syndrome / Q000188:drug therapy; D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D013927:Thrombosis / Q000188:drug therapy*; D000077486:Ticagrelor
C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077486:Ticagrelor; D000241:Adenosine