title: Outcomes with cangrelor versus clopidogrel on a background of bivalirudin: insights from the CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI]).
abstract: OBJECTIVE
  The aim of this study was to examine the efficacy and bleeding outcomes of cangrelor in patients in the CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI]) who underwent percutaneous coronary intervention with bivalirudin.
  
  
  BACKGROUND
  Cangrelor is a potent intravenous P2Y12 inhibitor with rapid onset and offset. In the CHAMPION PHOENIX, cangrelor compared with clopidogrel significantly reduced 48-h ischemic events including stent thrombosis, without increasing major bleeding. Bivalirudin has demonstrated ischemic outcomes similar to those with heparin plus glycoprotein IIb/IIIa inhibition, with reduced bleeding but increased early stent thrombosis.
  
  
  METHODS
  In the modified intent-to-treat population, 2,059 patients (18.8%) received bivalirudin, with 1,014 patients in the cangrelor treatment arm and 1,045 in the clopidogrel treatment arm.
  
  
  RESULTS
  At 48 h, the primary endpoint of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis was lower with cangrelor versus clopidogrel (48 [4.7%] vs. 70 [6.7%]; odds ratio [OR]: 0.68, p = 0.047). Death was similar in both arms (2 [0.2%] vs. 2 [0.2%]). Myocardial infarction was reduced by cangrelor (37 [3.6%] vs. 59 [5.6%]; OR: 0.63, p = 0.03), as was death/myocardial infarction (39 [3.8%] vs. 61 [5.8%]; OR: 0.65, p = 0.04). Cangrelor was associated with a nonsignificant trend toward less stent thrombosis (7 [0.7%] vs. 15 [1.4%]; OR: 0.48, p = 0.10), which was evident within 2 h after percutaneous coronary intervention (p = 0.057). GUSTO (Global Use of Strategies to Open Occluded Arteries) severe bleeding was similar in both arms (2 of 1,021 [0.2%] vs. 2 of 1,055 [0.2%]) as were other bleeding definitions and transfusions. Efficacy and safety results were consistent in patients with stable angina, non-ST-segment elevation acute coronary syndrome, and ST-segment elevation myocardial infarction (p for interaction: 0.62 and 0.29).
  
  
  CONCLUSIONS
  Cangrelor may offer an attractive benefit risk profile when used in combination with bivalirudin.
authors.affiliation: Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand. Electronic address: HarveyW@adhb.govt.nz.
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.affiliation: Brigham and Women's Hospital, Heart & Vascular Center, and Harvard Medical School, Boston, Massachusetts.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: Beth Israel Hospital, Boston, Massachusetts.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.affiliation: University of Giessen and Kerckhoff Heart Center, Bad Nauheim, Germany.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Hamm
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Scripps Clinic and Scripps Translational Science Institute, La Jolla, California.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Price
authors.affiliation: Institut National de la Santé et de la Recherche Médicale-Unité 114, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Paris, France; Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France; Royal Brompton Hospital, London, United Kingdom.
authors.forename: Ph Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Columbia University Medical Center and The Cardiovascular Research Foundation, New York, New York.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.affiliation: Interventional Cardiology, A.O. Fatebenefratelli, Bastioni di Porta Nuova, Milan, Italy.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Cortese
authors.affiliation: Cardiology PC, Birmingham, Alabama.
authors.forename: Michael
authors.initials: M
authors.lastname: Wilensky
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Efthymios N
authors.initials: EN
authors.lastname: Deliargyris
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Tiepu
authors.initials: T
authors.lastname: Liu
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Jayne
authors.initials: J
authors.lastname: Prats
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
mesh_terms: D000249:Adenosine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D003328:Coronary Thrombosis / Q000209:etiology / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D016017:Odds Ratio; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D015607:Stents; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D000249:Adenosine Monophosphate; C117446:cangrelor; D000077144:Clopidogrel; D013988:Ticlopidine; C074619:bivalirudin
keywords: CHAMPION PHOENIX; bivalirudin; cangrelor; stent thrombosis