Elsevier

The Lancet

Volume 355, Issue 9201, 29 January 2000, Pages 337-345
The Lancet

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

https://doi.org/10.1016/S0140-6736(99)11179-6Get rights and content

Summary

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.

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

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