Clopidogrel/Aspirin Interaction Study

Randomized, Factorial Study to Explore Interaction Between Aspirin and Clopidogrel in Stable Patients With Previous Myocardial Infarction or Coronary Artery Stent

This study will explore the effect of different doses of aspirin on the effects of double-dose or standard dose clopidogrel.

Study Hypothesis: Patients receiving double-dose compared with standard-dose clopidogrel will have increased blood concentrations of the active metabolite of clopidogrel and greater inhibition of ADP-induced platelet aggregation when also treated with acetylsalicylic acid (ASA) 325 mg/d as compared to ASA 81 mg/d.

Inclusion Criteria:

• > 1 month post myocardial infarction (MI), unstable angina or stent patients with stable condition
• Receiving regular ASA (81mg/d) and clopidogrel (75mg/d) for at least 1 week
• Written informed consent

Exclusion Criteria:

• Age < 18 years old
• Liver disease with transaminases and/or bilirubin > 1.5x upper limits of normal (ULN) (within 3 months of randomization)
• Renal impairment with creatinine clearance < 30 ml/min (within 3 months of randomization)
• Platelet count < 100x109/L and/or Hb< 100g/L (within 3 months of randomization)
• Use of oral anticoagulants or nonsteroidal antiinflammatory drug (NSAID) within the last 10 days or planned use during the study
• Use of antiplatelet agent other than aspirin and clopidogrel within the last 10 days
• High risk of bleeding (e.g. recent gastrointestinal bleeding, bleeding diathesis)
• Uncontrolled hypertension (> 180/110mmHg)
• Current smoker with ≥ 5 cigarettes/day
• Previously entered in this study or just finished other study within 2 weeks before recruitment
• Medical, geographic, or social factors making study participation impractical, or inability to provide written informed consent