title: Platelet inhibition with cangrelor in patients undergoing PCI.
abstract: BACKGROUND
  Cangrelor, a nonthienopyridine adenosine triphosphate analogue, is an intravenous blocker of the adenosine diphosphate receptor P2Y(12). This agent might have a role in the treatment of patients who require rapid, predictable, and profound but reversible platelet inhibition.
  
  
  METHODS
  We performed a large-scale international trial comparing cangrelor with 600 mg of oral clopidogrel administered before percutaneous coronary intervention (PCI) in patients with acute coronary syndromes. The primary efficacy end point was a composite of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours.
  
  
  RESULTS
  We enrolled 8877 patients, and 8716 underwent PCI. At 48 hours, cangrelor was not superior to clopidogrel with respect to the primary composite end point, which occurred in 7.5% of patients in the cangrelor group and 7.1% of patients in the clopidogrel group (odds ratio, 1.05; 95% confidence interval [CI], 0.88 to 1.24; P=0.59). Likewise, cangrelor was not superior at 30 days. The rate of major bleeding (according to Acute Catheterization and Urgent Intervention Triage Strategy criteria) was higher with cangrelor, a difference that approached statistical significance (3.6% vs. 2.9%; odds ratio, 1.26; 95% CI, 0.99 to 1.60; P=0.06), but this was not the case with major bleeding (according to the Thrombolysis in Myocardial Infarction criteria) or severe or life-threatening bleeding (according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria). A secondary exploratory end point of death from any cause, Q-wave myocardial infarction, or ischemia-driven revascularization showed a trend toward a reduction with cangrelor, but it was not significant (0.6% vs. 0.9%; odds ratio, 0.67; 95% CI, 0.39 to 1.14; P=0.14).
  
  
  CONCLUSIONS
  Cangrelor, when administered intravenously 30 minutes before PCI and continued for 2 hours after PCI, was not superior to an oral loading dose of 600 mg of clopidogrel, administered 30 minutes before PCI, in reducing the composite end point of death from any cause, myocardial infarction, or ischemia-driven revascularization at 48 hours. (ClinicalTrials.gov number, NCT00305162.)
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA. robert.harrington@duke.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
authors.forename: Steven
authors.initials: S
authors.lastname: McNulty
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
authors.forename: Charles V
authors.initials: CV
authors.lastname: Pollack
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Neal S
authors.initials: NS
authors.lastname: Kleiman
authors.forename: Shaun G
authors.initials: SG
authors.lastname: Goodman
authors.forename: Maged
authors.initials: M
authors.lastname: Amine
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Derek P
authors.initials: DP
authors.lastname: Chew
authors.forename: William J
authors.initials: WJ
authors.lastname: French
authors.forename: Franz
authors.initials: F
authors.lastname: Leisch
authors.forename: Keyur H
authors.initials: KH
authors.lastname: Parikh
authors.forename: Simona
authors.initials: S
authors.lastname: Skerjanec
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D000249:Adenosine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000284:Administration, Oral; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000077144:Clopidogrel; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019233:Retreatment; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D010975:Platelet Aggregation Inhibitors; D000249:Adenosine Monophosphate; C117446:cangrelor; D000077144:Clopidogrel; D013988:Ticlopidine