The fall and rise of cangrelor

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)526-532
Number of pages7
JournalDrug Development Research
Volume74
Issue number8
DOIs
Publication statusPublished - Dec 2013

Fingerprint

Myocardial Infarction
Percutaneous Coronary Intervention
clopidogrel
Purinergic P2Y Receptor Antagonists
Blood Platelets
Randomized Controlled Trials
Medical Futility
cangrelor
Cardiac Catheterization
Biomarkers
Therapeutics

Keywords

  • cangrelor
  • clinical event committee
  • myocardial infarction
  • randomized controlled trial

ASJC Scopus subject areas

  • Drug Discovery

Cite this

The fall and rise of cangrelor. / Leonardi, Sergio; Ferlini, Marco; Marino, Marcello; Visconti, Luigi Oltrona.

In: Drug Development Research, Vol. 74, No. 8, 12.2013, p. 526-532.

Research output: Contribution to journalArticle

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