Sibrafiban.

Sibrafiban is the orally administered, nonpeptide, double-prodrug of Ro 44-3888 which is a selective glycoprotein IIb/IIIa receptor antagonist. It is currently undergoing clinical trials for secondary prevention of cardiac events in patients stabilised after acute coronary syndromes. In a phase II dose-finding study (TIMI 12) in patients stabilised after a myocardial infarction (MI) or an episode of unstable angina, there was a dose-dependent inhibition of platelet aggregation which correlated closely with the plasma concentration of the total active drug. An ongoing phase III study (SYMPHONY) compares the effects of sibrafiban on cardiac events with that of aspirin in patients stabilised after a Q wave MI or an episode of unstable angina. This large trial uses twice daily dosage regimens to produce the plasma concentrations which were associated with less bleeding in the earlier dose-ranging trial. A long term (minimum duration 12 months) phase III study (2nd SYMPHONY) is under way to compare the effects of sibrafiban on cardiac events with those of aspirin in patients stabilised after an MI or an episode of unstable angina. The most common adverse events associated with sibrafiban include bleeding, with minor haemorrhages occurring more often than with aspirin.