Oral glycoprotein IIb/IIIa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial

Background-Although intravenous glycoprotein IIb/IIIa inhibitors are benefi cial in patients with acute coronary syndromes, prolonged oral IIb/IIIa inh ibition might provide an additional reduction in recurrent events. Methods and Results-Investigators at 888 hospitals in 29 countries enrolled 10 288 patients with acute coronary syndromes, which was defined as ischem ic pain at rest within 72 hours of randomization, associated with positive cardiac markers, electrocardiographic changes, or prior cardiovascular dise ase. Patients received aspirin and were randomized to receive, for the dura tion 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 twi ce daily (50/30 group), or (3) a placebo, The primary composite end point w as death, myocardial infarction, recurrent ischemia requiring rehospitaliza tion, urgent revascularization, or stroke. The trial was terminated prematu rely because of an unexpected increase in 30-day mortality in the 50/30 orb ofiban group. Mortality through 10 months was 3.7% for the placebo group ve rsus 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 sever e 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, respect ively, Exploratory subgroup analyses found that patients who underwent perc utaneous coronary intervention had a lower mortality and a significant redu ction in the composite end point (P=0.001) with orbofiban. Conclusions-Fixed-dose orbofiban failed to reduce major cardiovascular even ts and was associated with increased mortality in this broad population of patients with acute coronary syndromes; however, a benefit was observed amo ng patients who underwent percutaneous coronary intervention.