title: The failure of orally administered glycoprotein IIb/IIIa inhibitors to prevent recurrent cardiac events.
abstract: OBJECTIVE
  Despite the success of intravenous glycoprotein IIb/IIIa antagonists, oral formulations have failed to show benefit and have been associated with increased mortality. To understand these findings, we performed a meta-analysis of results from four phase 3 trials.
  
  
  METHODS
  Trials were identified by MEDLINE search; review of abstracts from American College of Cardiology, European Society of Cardiology, and American Heart Association scientific sessions; or querying investigators in the field. Published, phase 3, randomized, placebo-controlled trials involving more than 1000 patients with coronary artery disease that compared an oral glycoprotein IIb/IIIa antagonist with or without background aspirin versus aspirin, and that had a planned follow-up of > or =30 days, were included. Four trials met these criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were generated from results, and combined using an empirical Bayes random-effects model.
  
  
  RESULTS
  Among 33,326 patients, oral glycoprotein IIb/IIIa agents were associated with 31% increased mortality (OR = 1.31; 95% CI: 1.12 to 1.53; P= 0.0001). Results were similar whether the agent was added to (OR = 1.38; 95% CI: 1.15 to 1.67) or substituted for (OR = 1.37; 95% CI: 1.00 to 1.86) aspirin. Ischemic events or sudden death (OR = 1.22; 95% CI: 0.91 to 1.63) were also more common. Among patients with acute coronary syndromes, the incidence of myocardial infarction was increased (OR = 1.16; 95% CI: 1.03 to 1.29).
  
  
  CONCLUSIONS
  Oral glycoprotein IIb/IIIa inhibitor therapy is associated with increased mortality and myocardial infarction. No single explanation for these findings is satisfactory; the problem is likely to be multifactorial.
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina 27707, USA.
authors.forename: L Kristin
authors.initials: LK
authors.lastname: Newby
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: R John
authors.initials: RJ
authors.lastname: Simes
authors.forename: Vic
authors.initials: V
authors.lastname: Hasselblad
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
mesh_terms: D000284:Administration, Oral; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use*; D003327:Coronary Disease / Q000150:complications / Q000401:mortality / Q000517:prevention & control*; D016757:Death, Sudden, Cardiac; D006801:Humans; D009203:Myocardial Infarction / Q000209:etiology; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D016032:Randomized Controlled Trials as Topic; D017211:Treatment Failure
chemical_list: D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D001241:Aspirin