Authors
Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators
Title
Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes Without ST-Segment Elevation
References
N Engl J Med 2001;345:494-502.
Background
Despite use of heparin and aspirin in acute coronary syndromes without ST-segment elevation, risk of major vascular events remains high. It is unknown if addition of clopidogrel to standard therapy will improve outcomes.
Purpose
To compare the efficacy and safety of early and long-term use of clopidogrel plus aspirin to aspirin alone in patients with acute coronary syndromes without ST-elevation.
Design
Multicenter, Randomized, double-blind, placebo controlled trial 12, 562 patients who presented within 24 hours after the onset of symptoms of acute coronary syndrome (without ST-elevation)
Exclusion Criteria
None.
Follow-Up
3-12 months (mean duration: 9 months)
Treatment Regimen
Clopidogrel 300 mg or matching placebo, then clopidogrel 75 mg po once daily (or matching placebo). Aspirin 75-325 mg daily was given to all patients.
Results
Clopidogrel resulted in a significant reduction in the primary outcome, including a reduction in non-fatal myocardial infarction rate. Clopidogrel resulted in a significant reduction in the primary outcome, including a reduction in non-fatal myocardial infarction rate. Major and minor bleeding was significantly higher in the clopidogrel group. The excess major bleeding episodes were due to gastrointestinal hemorrahges and bleeding at the sites of arterial punctures. There was no excess rate of fatal bleeding, bleeding requiring surgical intervention, or hemorrhagic stroke.
Summary
Addition of clopidogrel to early and long-term aspirin reduced the composite endpoint of death from cardiovascular causes, non-fatal MI, or stroke and reduced the primary endpoint or refractory ischemia. The benefits were at a cost of increased major (non life-threatening) and minor bleeding.
Implications
None.
Related Figures
[1, 3]