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.
Capodanno
Davide
D
University of Florida College of Medicine, Jacksonville, FL 32209, USA. dominick.angiolillo@jax.ufl.edu
Dharmashankar
Kodlipet
K
Angiolillo
Dominick J
DJ
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