Funding: No extramural funding was used to support this work.
The Fall and Rise of Cangrelor
Article first published online: 31 OCT 2013
© 2013 Wiley Periodicals, Inc.
Drug Development Research
Special Issue: Thrombosis Drugs and Diagnostics. Part II
Volume 74, Issue 8, pages 526–532, December 2013
How to Cite
Leonardi, S., Ferlini, M., Marino, M. and Visconti, L. O. (2013), The Fall and Rise of Cangrelor. Drug Dev. Res., 74: 526–532. doi: 10.1002/ddr.21111
- Issue published online: 13 DEC 2013
- Article first published online: 31 OCT 2013
- myocardial infarction;
- randomized controlled trial;
- clinical event committee
|Clinical Development Phases I-III Regulatory, Quality, Manufacturing|
The antagonism of the platelet P2Y12 receptor is essential for the treatment of patients undergoing percutaneous coronary intervention (PCI). Cangrelor is an intravenous P2Y12 receptor antagonist that being both reversible and very short acting has the potential to overcome some of the limitations of currently available oral agents like clopidogrel, prasugrel, and ticagrelor. Cangrelor has been studied in a large phase III program called Cangrelor versus standard therapy to acHieve optimal Management of Platelet InhibitiON (CHAMPION) that included three randomized controlled trials (RCTs): PCI, PLATFORM, and PHOENIX. The first two RCTs, conducted concurrently, were prematurely interrupted for futility. However, it was soon evident that unanticipated challenges in the ascertainment of PCI-related myocardial infarction (MI) due to shorter-than-expected times to cardiac catheterization may have reduced the ability to detect cangrelor efficacy. While CHAMPION PCI and PLATFORM were ongoing, the universal definition of MI provided recommendations to address these challenges. Specifically, this consensus document recommended the presence of a rise and/or a fall of cardiac biomarkers to define MI. The universal MI definition enhanced by novel approaches to efficiently and accurately implement this definition was used to adjudicate MI in PHOENIX, which showed superiority of cangrelor over clopidogrel, with an effect that was mostly evident in MI. The development of cangrelor illustrates the critical importance of PCI-related MI as end point, the challenges in its definition in patients undergoing a very early invasive management, and the role of the universal MI definition in overcoming these challenges.