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Updated: Jun 11, 2026
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists: a meta-analysis of phase III multicenter
1Department of Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Background:
Numerous clinical trials have established the benefits of intravenous glycoprotein IIb/IIIa inhibition in the management of coronary artery disease. In contrast, the recent large-scale, placebo-controlled, randomized trials of the oral glycoprotein IIb/IIIa antagonists have failed to provide commensurate reductions in late composite ischemic end points despite potent inhibition of platelet aggregation.
Methods And Results:
The ORs for death, myocardial infarction, urgent revascularization, and major bleeding from the 4 large-scale, placebo-controlled, randomized trials with oral glycoprotein IIb/IIIa inhibitors were calculated and combined. Stratification by low-dose or high-dose therapy and the use of concurrent aspirin was also undertaken. In 33 326 patients followed for >30 days, a consistent and statistically significant increase in mortality was observed with oral glycoprotein IIb/IIIa therapy (OR, 1.37; 95% CI, 1.13 to 1.66; P:=0.001). This effect was evident regardless of aspirin coadministration and treatment with either low-dose or high-dose therapy. Although a reduction in urgent revascularization was observed with oral glycoprotein IIb/IIIa inhibition, pooled analysis favored an increase in myocardial infarction that did not demonstrate statistical significance.
Conclusions:
Although we found a highly significant excess in mortality consistent across 4 trials with 3 different oral glycoprotein IIb/IIIa inhibitor agents, this was associated with a reduction in the need for urgent revascularization and no increase in myocardial infarction. These findings suggest the potential for a direct toxic effect with these agents and argue against a prothrombotic mechanism. Further investigation to elucidate the cause of this increased fatality risk is warranted.
Insights
Oral glycoprotein IIb/IIIa inhibitors in coronary artery disease management increased mortality risk, despite reducing urgent revascularization needs. Further research is needed to understand this increased fatality risk associated with these antiplatelet agents.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Intravenous glycoprotein IIb/IIIa inhibitors are beneficial for coronary artery disease.
- Oral glycoprotein IIb/IIIa antagonists have not shown comparable benefits in large trials.
- Platelet aggregation inhibition by oral agents has not translated to reduced ischemic events.
Purpose of the Study:
- To evaluate the safety and efficacy of oral glycoprotein IIb/IIIa inhibitors.
- To analyze outcomes from large-scale, placebo-controlled trials of oral glycoprotein IIb/IIIa antagonists.
- To investigate the impact of these agents on mortality, myocardial infarction, and revascularization.
Main Methods:
- Pooled analysis of 4 large-scale, placebo-controlled, randomized trials.
- Inclusion of 33,326 patients with follow-up >30 days.
- Calculation and stratification of odds ratios (ORs) for key clinical end points, including mortality, myocardial infarction, urgent revascularization, and major bleeding, by therapy dose and aspirin use.
Main Results:
- A statistically significant increase in mortality was observed with oral glycoprotein IIb/IIIa therapy (OR, 1.37; P:=0.001).
- This increased mortality risk was consistent across different agents, doses, and with or without aspirin.
- A reduction in urgent revascularization was noted, but no significant increase in myocardial infarction was detected.
Conclusions:
- Oral glycoprotein IIb/IIIa inhibitors are associated with a significant excess in mortality.
- The observed mortality increase may indicate a direct toxic effect rather than a prothrombotic mechanism.
- Further investigation is warranted to determine the cause of the increased fatality risk with these agents.
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