Cangrelor: a review on its mechanism of action and clinical development

Abstract

In patients with acute coronary syndromes and undergoing percutaneous coronary intervention, numerous large-scale clinical trials have shown that adjunctive treatment with the P2Y₁₂ receptor antagonist clopidogrel in addition to aspirin reduces ischemic events. These studies underscore the importance of blockade of the P2Y₁₂ signaling pathway in these settings. However, recent findings have shown that clopidogrel therapy may have some shortcomings. These include its broad range of interindividual-response profiles, where patients with low P2Y₁₂ inhibitory effects have an increased risk of recurrent ischemic events, including stent thrombosis, and its irreversible mechanism of action. These observations underscore the need for novel antiplatelet agents overcoming these limitations. Cangrelor (AR-C69931MX) is an intravenous, direct-acting and reversible P2Y₁₂ receptor antagonist. Cangrelor has a rapid onset and offset of action and achieves significantly greater degrees of platelet inhibition compared with clopidogrel. This article provides an overview of the current status of knowledge on cangrelor, focusing on its pharmacologic properties, clinical development and potential future applications.

Keywords::

• acute coronary syndrome
• antiplatelet
• antithrombotic
• cangrelor
• percutaneous coronary intervention

Financial & competing interests disclosure

Dominick J Angiolillo has received honoraria or given lectures for: Bristol Myers Squibb; Sanofi-Aventis; Eli Lilly Co; and Daiichi Sankyo, Inc. He has also received honoraria or been on the advisory board for: Bristol Myers Squibb; Sanofi-Aventis; Eli Lilly Co; Daiichi Sankyo, Inc.; The Medicines Company; Portola; Novartis; Medicure; Accumetrics; Arena Pharmaceuticals; and Astra Zeneca. He has received research grants from: GlaxoSmithKline; Otsuka; Eli Lilly Co; Daiichi Sankyo, Inc., The Medicines Company; Portola; Accumetrics; Schering-Plough; Astra-Zeneca; Eisai; 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.