title: Oral glycoprotein IIb/IIIa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial.
abstract: BACKGROUND
  Although intravenous glycoprotein IIb/IIIa inhibitors are beneficial in patients with acute coronary syndromes, prolonged oral IIb/IIIa inhibition might provide an additional reduction in recurrent events.
  
  
  RESULTS
  Investigators at 888 hospitals in 29 countries enrolled 10 288 patients with acute coronary syndromes, which was defined as ischemic pain at rest within 72 hours of randomization, associated with positive cardiac markers, electrocardiographic changes, or prior cardiovascular disease. Patients received aspirin and were randomized to receive, for the duration of the trial, (1) 50 mg of orbofiban twice daily (50/50 group), (2) 50 mg of orbofiban twice daily for 30 days followed by 30 mg of orbofiban twice daily (50/30 group), or (3) a placebo. The primary composite end point was death, myocardial infarction, recurrent ischemia requiring rehospitalization, urgent revascularization, or stroke. The trial was terminated prematurely because of an unexpected increase in 30-day mortality in the 50/30 orbofiban group. Mortality through 10 months was 3.7% for the placebo group versus 5.1% in the 50/30 group (P=0.008) and 4.5% in the 50/50 group (P=0.11). There were no differences in the primary end point (22.9%, 23.1%, and 22.8%, for the placebo, 50/30, and 50/50 groups, respectively). Major or severe bleeding (but not intracranial hemorrhage) was higher with orbofiban; it occurred in 2. 0%, 3.7% (P=0.0004), and 4.5% (P<0.0001) of patients, respectively. Exploratory subgroup analyses found that patients who underwent percutaneous coronary intervention had a lower mortality and a significant reduction in the composite end point (P=0.001) with orbofiban.
  
  
  CONCLUSIONS
  -Fixed-dose orbofiban failed to reduce major cardiovascular events and was associated with increased mortality in this broad population of patients with acute coronary syndromes; however, a benefit was observed among patients who underwent percutaneous coronary intervention.
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02115, USA. ccannon@rics.bwh.harvard.edu
authors.forename: C P
authors.initials: CP
authors.lastname: Cannon
authors.forename: C H
authors.initials: CH
authors.lastname: McCabe
authors.forename: R G
authors.initials: RG
authors.lastname: Wilcox
authors.forename: A
authors.initials: A
authors.lastname: Langer
authors.forename: A
authors.initials: A
authors.lastname: Caspi
authors.forename: P
authors.initials: P
authors.lastname: Berink
authors.forename: J
authors.initials: J
authors.lastname: Lopez-Sendon
authors.forename: J
authors.initials: J
authors.lastname: Toman
authors.forename: A
authors.initials: A
authors.lastname: Charlesworth
authors.forename: R J
authors.initials: RJ
authors.lastname: Anders
authors.forename: J C
authors.initials: JC
authors.lastname: Alexander
authors.forename: A
authors.initials: A
authors.lastname: Skene
authors.forename: E
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000284:Administration, Oral; D000409:Alanine / Q000008:administration & dosage / Q000009:adverse effects; D000925:Anticoagulants / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage; D003327:Coronary Disease / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000009:adverse effects; D020521:Stroke / Q000188:drug therapy; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011759:Pyrrolidines; D006493:Heparin; C120234:orbofiban; D000409:Alanine; D001241:Aspirin