Authors
Steinhubl SR, Berger PB, Mann JT, et al.
Title
Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention.
References
JAMA 2002;288:2411-2420.
Background
Addition of clopidogrel to aspirin post percutaneous coronary intervention (PCI) decreases thrombotic complications, however the optimal timing of initiation of clopidogrel and duration of therapy is not known.
Purpose
To determine the benefit and risks of 12 month treatment with clopidogrel added to aspirin after PCI and whether an initial loading dose of clopidogrel is effective and safe.
Design
  • Randomized, double-blind, placebo-controlled trial
  • 2,116 patients planned for elective PCI or at high likelihood for requiring PCI.
Exclusion Criteria
None.
Follow-Up
1 year
Treatment Regimen
  • Clopidogrel 300 mg loading dose 3-24 hours prior to PCI or matching placebo (all patients received aspirin 325 mg).
  • Clopidogrel 75 mg daily and aspirin 325 mg daily in both groups post-PCI (up to day 28)
  • From day 29 to 12 months, the pre-treatment group continued clopidogrel 75 mg daily and the no pre-treatment group received matching placebo.
  • Post-PCI, all patients received 81-325 mg daily
Results
Primary Endpoints:
  1. Composite of death, myocardial infarction, or urgent target vessel revascularization at 28 days
  2. Composite of death, myocardial infarction, or stroke at 1 year.

Long-term treatment with clopidogrel significantly reduced the primary composite endpoint by 26.9%. Clopidogrel pre-treatment dosing did not decrease the composite of death, myocardial infarction, or urgent target vessel revascularization at 28 days. However when analyzed according to timing of loading dose, patients who received clopidogrel loading dose at least 6 hours before PCI had a risk reduction of 38.6%.

Patients treated with clopidogrel for 1 year had a non-significant increase in major bleeding compared to placbo (8.8% vs 6.7%;p=0.07).
Summary
Long-term (1 year) clopidogrel therapy in addition to aspirin post-PCI decreased the risk of ischemic events. Clopidogrel loading dose given at least 3 hours before PCI did not reduce events at 28 days, however data suggests that benefit may occur if the loading dose given at least 6 hours before the procedure in patients planned for elective PCI.
Implications
None.
Related Figures
[4]