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

Lancet. 2000 Jan 29;355(9201):337-45.

Abstract

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% 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%]).

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Angina, Unstable / prevention & control*
  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Oximes / administration & dosage*
  • Oximes / adverse effects
  • Piperidines / administration & dosage*
  • Piperidines / adverse effects
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Recurrence

Substances

  • Oximes
  • Piperidines
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Aspirin
  • sibrafiban