Mechanism of action and clinical development of ticagrelor, a novel platelet ADP P2Y₁₂ receptor antagonist

Abstract

Inhibition of the platelet ADP P2Y₁₂ 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 P2Y₁₂ 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 P2Y₁₂ 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.

Keywords::

• acute coronary syndromes
• platelet
• ticagrelor

Financial & competing interests disclosure

Dominick J Angiolillo receives honoraria from and provides lectures to Bristol Myers Squibb, Sanofi-aventis, Eli Lilly and Company, and Daiichi Sankyo, Inc. He is also on the advisory board at Bristol Myers Squibb, Sanofi-aventis, Eli Lilly and Company, Daiichi Sankyo, Inc., AstraZeneca, The Medicines Company, Portola Pharmaceuticals, Novartis and Arena Pharmaceuticals. In addition, Dominick J Angiolillo has received research grants from GlaxoSmithKline, Otsuka, Accumetrics, Eli Lilly and Company, Daiichi Sankyo, Inc., The Medicines Company, AstraZeneca, Eisai, Portola Pharmaceuticals, Schering-Plough, and Johnson and Johnson. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.