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. Methods and 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.

Differential Expression of Cardiac Biomarkers by Gender in Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction

“…Each of the components of this end point was adjudicated by an independent clinical events committee using standard TIMI definitions. 26 Baseline biomarkers were considered positive if above an accepted, prespecified cut point based on prior work. Specifically, cut points for positive biomarkers were 0.01 ng/mL for cardiac TnT, 14 0.1 ng/mL for TnI, 14 15 mg/L for hs-CRP, 21 and 80 pg/mL for BNP.…”

“…Details of the TIMI 11 studies have been published elsewhere 28,29 ; each compared unfractionated heparin to enoxaparin. Details of the OPUS-TIMI 16 trial, 26 a randomized, placebocontrolled trial of orbofiban (oral glycoprotein IIb/IIIa inhibitor) in ACS have also been published previously. The present analysis was limited to patients with UA/NSTEMI.…”

Peptídeo natriurético tipo-B e doenças cardiovasculares

“…Uma análise de subgrupos do estudo OPUS TIMI 16 revelou que níveis mais elevados de peptídeo natriurético tipo-B estavam associados com estenoses coronarianas > 50% e com testes de esforço positivo (p<0,001) 31 .…”

Does initial and delayed heart rate predict mortality in patients with acute coronary syndromes?

“…The protocol and main results of the OPUS-TIMI-16 trial have been reported previously. 11 Briefly, the study was designed to compare two doses of the oral glycoprotein IIb/IIIa platelet receptor blocker, orbofiban, with placebo for management of patients with ACS. In all, 10,302 patients were randomized into the trial within 72 h of the onset of ACS from October 10, 1997, to November 5, 1998.…”

“…In all, 10,302 patients were randomized into the trial within 72 h of the onset of ACS from October 10, 1997, to November 5, 1998. The exclusion criteria were reported previously 11 and included patients with cardiogenic shock. All patients received aspirin; other therapy was at the discretion of the attending physician.…”