ArticlesComparison of sibrafiban with aspirin for prevention of cardiovascular events after acute coronary syndromes: a randomised trial*
Introduction
Aspirin is effective in the secondary prevention of ischaemic events for patients with unstable angina or myocardial infarction (acute coronary syndromes), but the fact that deaths and myocardial infarctions occur even in aspirin-treated patients suggests the need for more potent antiplatelet therapy.1 Intravenous antagonists of the platelet glycoprotein IIb/IIIa receptor, the final common pathway for platelet aggregation, are effective for the acute management of such patients.2, 3, 4, 5 Whether longterm, oral treatment with blockers of the glycoprotein IIb/IIIa receptor would provide benefit has not yet been established. We undertook an international, double-blind, randomised comparison of two dose regimens of sibrafiban (a potent oral glycoprotein IIb/IIIa inhibitor) and aspirin in patients after an acute coronary syndrome. The primary objective was to compare the efficacy, safety, and tolerability of these three strategies over 90 days of treatment. We report the primary results of the trial.
Section snippets
Study population
The complete methods of the SYMPHONY (Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes) trial have been published.6 The main inclusion criterion was chest pain or anginal-equivalent symptoms lasting at least 20 min. Participants also had to have one of: creatine kinase MB above the upper limit of normal, total creatine kinase twice the upper limit of normal, or troponin I or T above the upper limit of normal if neither creatine
Results
Of the 9233 patients enrolled, 3089 were assigned aspirin, 3105 low-dose sibrafiban, and 3039 high-dose sibrafiban (figure 1). Baseline characteristics were well balanced, with no differences among the treatment groups (table 1). Nearly 75% of patients had myocardial infarction as the qualifying event, and randomised treatment was assigned a median of 3·5 days (IQR 2·3–5·1) after the qualifying event.
Overall, 78·2% of patients completed the protocol-specified course of therapy, with a median
Discussion
The two different dosing strategies of the oral platelet glycoprotein IIb/IIIa inhibitor sibrafiban did not lower the rates of adverse clinical outcomes compared with aspirin, despite definite evidence that sibrafiban is a more potent inhibitor of platelet aggregation than is aspirin. The sibrafiban doses used produce substantial inhibition of ADP-induced platelet aggregation.7 Furthermore, preliminary pharmacokinetic data suggest that more than 90% of patients in this trial had sibrafiban
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Study organisation and investigators given at end of paper