Comparison of sibrafiban with aspirin for prevention of cardiovascular events after acute coronary syndromes: A randomised trial

Background: Aspirin lowers risks of death and myocardial infarction in patients with acute coronary syndromes. Intravenous glycoprotein IIb/IIIa receptor antagonists further reduce the rates of ischaemic events in these patients, but the efficacy of long-term oral glycoprotein IIb/IIIa receptor blockade has not been established. We tested whether the oral glycoprotein IIb/IIIa receptor antagonist sibrafiban would prevent more cardiovascular events than aspirin, when given within 7 days of, and sustained for 90 days after, an acute coronary syndrome event. Methods: 9233 patients who had stabilised after an acute coronary syndrome event were randomly assigned aspirin (80 mg orally twice daily) or low-dose or high-dose sibrafiban. Sibrafiban doses (3.0 mg, 4.5 mg, or 6.0 mg) were based on a model accounting for weight and serum creatinine and designed to achieve at least 25% steady-state inhibition of platelet aggregation (low dose) or at least 50% inhibition (high dose). The primary endpoint was the composite of death, non-fatal infarction or reinfarction, or severe recurrent ischaemia at 90 days. Analysis was by intention to treat. Findings: The 90-day rate of the primary endpoint did not differ significantly between the groups assigned aspirin (302 [9.8%]), low-dose sibrafiban (310 [10.1%]; odds ratio 1.03 [95% Cl 0.87-1.21]), and high-dose sibrafiban (303 [10.1%]; 1.03 [0.87-1.21]). The groups did not differ significantly in the rates of the component events or secondary efficacy endpoints. Major bleeding was more common with high-dose sibrafiban (171 [5.7%]) than with aspirin (120 [3.9%]) or low-dose sibrafiban (159 [5.2%]). Interpretation: Sibrafiban showed no additional benefit over aspirin for secondary prevention of major ischaemic events after an acute coronary syndrome, and was associated with more dose-related bleeding.