Optimizing the Use of Cangrelor in the Real World

Arman Qamar; Deepak L. Bhatt

Disclosures

Am J Cardiovasc Drugs. 2017;17(1):5-16. 

In This Article

Cangrelor: Pharmacologic Characteristics

Cangrelor is a highly potent, intravenously administered, platelet P2Y12 receptor inhibitor that directly blocks adenosine diphosphate (ADP)-induced platelet aggregation and activation. It provides rapid onset and sustained platelet inhibition that is quickly reversible following discontinuation of cangrelor infusion.[37,38] For example, in healthy volunteers, a 30-μg/kg bolus followed by a 4-μg/kg/min continuous infusion achieved at least over 90 % inhibition of platelet aggregation within 2 min of bolus administration, and this was maintained throughout the infusion.[39] Following termination of the infusion, platelet function returned to baseline in approximately 60 min. Unlike clopidogrel and prasugrel, cangrelor is not a prodrug and does not require metabolic activation for antiplatelet effect. The plasma half-life of cangrelor is 3–5 min, and platelet function returns to normal within 1 h after stopping the infusion. In contrast to intravenous antiplatelet therapy with glycoprotein IIb/IIIa receptor inhibitors, cangrelor overdosing is not associated with increased bleeding, a favorable effect attributed to its very short half-life and rapid offset of action.[40] Similar to other P2Y12 receptor inhibitors, the most common side effect associated with cangrelor is bleeding. The other reported adverse effect of cangrelor is dyspnea, though very uncommon and rarely leads to discontinuation. Transient dyspnea is a well known side effect of reversible platelet ADP-receptor antagonists that may influence other adenosine-mediated pathways, and has previously been reported with ticagrelor. In phase I and phase II studies, cangrelor safety, pharmacokinetics, and pharmacodynamics were not affected by age, hepatic, or renal function. Thus, no dose adjustments are needed in older patients or in patients with liver or kidney disease. Given its favorable pharmacologic profile, cangrelor can fill the gaps in the antithrombotic therapy of patients with ACS and those undergoing PCI.

Thus far, the use of cangrelor as a periprocedural antiplatelet agent in patients undergoing PCI has been investigated in three phase III clinical trials: Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION) PCI, CHAMPION PLATFORM, and CHAMPION PHOENIX[41–44] ( Table 1 ). The CHAMPION PCI and PLATFORM trials examined the role of cangrelor compared with clopidogrel in patients with stable angina or ACS who were treated with PCI. Both trials were prematurely terminated for their futility regarding reducing their primary composite end point of death from any cause, MI, or ischemia-driven revascularization (IDR) at 48 h. However, in a prespecified pooled analysis of the CHAMPION PCI and CHAMPION PLATFORM data using the universal definition of MI instead of the trial definition, treatment with cangrelor compared with clopidogrel significantly reduced the rates of periprocedural ischemic events, including stent thrombosis, with no increase in severe bleeding.[45] These findings were further investigated in the CHAMPION PHOENIX trial.

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