Comparison of sibrafiban with aspirin for prevention of cardiovascular events after acute coronary syndromes: a randomised trial. The SYMPHONY Investigators. Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes.
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.


RESULTS
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% CI 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%]).


CONCLUSIONS
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.
D000284:Administration, Oral; D000368:Aged; D000789:Angina, Unstable / Q000517:prevention & control*; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010091:Oximes / Q000008:administration & dosage* / Q000009:adverse effects; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D012008:Recurrence
D010091:Oximes; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D001241:Aspirin; C100917:sibrafiban