Abstract
Purpose
Despite the success of intravenous glycoprotein IIb/IIIa antagonists, oral formulations
have failed to show benefit and have been associated with increased mortality. To
understand these findings, we performed a meta-analysis of results from four phase
3 trials.
Subjects and methods
Trials were identified by MEDLINE search; review of abstracts from American College
of Cardiology, European Society of Cardiology, and American Heart Association scientific
sessions; or querying investigators in the field. Published, phase 3, randomized,
placebo-controlled trials involving more than 1000 patients with coronary artery disease
that compared an oral glycoprotein IIb/IIIa antagonist with or without background
aspirin versus aspirin, and that had a planned follow-up of ≥30 days, were included.
Four trials met these criteria. Odds ratios (ORs) and 95% confidence intervals (CIs)
were generated from results, and combined using an empirical Bayes random-effects
model.
Results
Among 33,326 patients, oral glycoprotein IIb/IIIa agents were associated with 31%
increased mortality (OR = 1.31; 95% CI: 1.12 to 1.53; P= 0.0001). Results were similar whether the agent was added to (OR = 1.38; 95% CI:
1.15 to 1.67) or substituted for (OR = 1.37; 95% CI: 1.00 to 1.86) aspirin. Ischemic
events or sudden death (OR = 1.22; 95% CI: 0.91 to 1.63) were also more common. Among
patients with acute coronary syndromes, the incidence of myocardial infarction was
increased (OR = 1.16; 95% CI: 1.03 to 1.29).
Conclusions
Oral glycoprotein IIb/IIIa inhibitor therapy is associated with increased mortality
and myocardial infarction. No single explanation for these findings is satisfactory;
the problem is likely to be multifactorial.
Keywords
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Article info
Footnotes
Drs. Newby, Califf, White, Harrington, Van de Werf, Granger, Simes, and Armstrong received research grant support for SYMPHONY and 2nd SYMPHONY from F. Hoffmann-La Roche Ltd, Basal, Switzerland. Dr. Van de Werf serves on the speakers bureau for F. Hoffmann-La Roche Ltd. Drs. Califf and Harrington received research grant support for BRAVO from SmithKline Beecham, Collegeville, Pennsylvania.
Identification
Copyright
© 2002 Excerpta Medica Inc. Published by Elsevier Inc. All rights reserved.
