title: Cangrelor With and Without Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing Percutaneous Coronary Intervention.
abstract: BACKGROUND
  Cangrelor, an intravenous, reversible P2Y12antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI).
  
  
  OBJECTIVE
  This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs).
  
  
  METHODS
  This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator's discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization.
  
  
  RESULTS
  Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint= 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint= 0.21). GPI use was associated with increased risk of bleeding in both treatment arms.
  
  
  CONCLUSIONS
  Cangrelor's efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571).
authors.affiliation: Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Muthiah
authors.initials: M
authors.lastname: Vaduganathan
authors.affiliation: Stanford University Medical School, Stanford, California.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
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: The Medicines Company, Parsippany, New Jersey.
authors.forename: Efthymios N
authors.initials: EN
authors.lastname: Deliargyris
authors.affiliation: FACT (French Alliance for Cardiovascular clinical Trials), DHU FIRE, INSERM Unité 1148, Université Paris-Diderot, and Hôpital Bichat, Assistance-Publique-Hôpitaux de Paris, Paris, France; NHLI, Imperial College, Royal Brompton Hospital, London, United Kingdom.
authors.forename: Ph Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.affiliation: Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Hamm
authors.affiliation: Scripps Clinic and Scripps Translational Science Institute, La Jolla, California.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Price
authors.affiliation: Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Menozzi
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Jayne
authors.initials: J
authors.lastname: Prats
authors.affiliation: The Medicines Company, Parsippany, New Jersey.
authors.forename: Steven
authors.initials: S
authors.lastname: Elkin
authors.affiliation: Stanford University Medical School, Stanford, California.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Green Lane Cardiovascular Service, Auckland, New Zealand.
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. Electronic address: dlbhattmd@post.harvard.edu.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
mesh_terms: D000249:Adenosine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D000077144:Clopidogrel; D015331:Cohort Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000249:Adenosine Monophosphate; C117446:cangrelor; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: antiplatelet therapy; bleeding; coronary artery disease; outcomes