Clopidogrel and aspirin are commonly used in combination to prevent heart attacks and to prevent blockage of stents. Both clopidogrel and aspirin work by preventing platelets (sticky cells that circulate in the blood) from forming blood clots in the arteries supplying oxygen to the heart and in stents. The investigators hypothesize that aspirin 325mg compared with aspirin 81 mg will increase blood levels of the active metabolite of clopidogrel in patients with a history of coronary artery disease who receive a 600mg loading dose of clopidogrel.

Eligible patients will be randomized to receive clopidogrel 600mg + aspirin 325mg (Group A) or clopidogrel 600mg + aspirin 81mg (Group B). Patients will be fasted for at least 8 hours prior to study drug administration. Blood samples will be collected at 1 hour after study drug administration for measurement of clopidogrel active metabolite levels and genotyping.

Inclusion Criteria:

• Stable patients >1 month post ACS (including ST elevated myocardial infarction, non-ST elevated myocardial infarction or unstable angina) or stent
• Receiving regular ASA (81mg/d) and clopidogrel (75mg/d) for at least 1 week
• Written informed consent

Exclusion Criteria:

• Age < 18 years

• Liver disease with ALT or bilirubin >2x upper limits of normal (ULN)*

• Renal impairment with creatinine clearance <30 ml/min*

• Deemed to be at high risk of bleeding (e.g., recent bleeding, platelet count<100x109/L or hemoglobin <100g/L)*

• Anticoagulant or NSAID therapy within the last 5 days

• Antiplatelet agent other than aspirin and clopidogrel within the last 10 days

• Uncontrolled hypertension (>=180/110mmHg)

  • within 3 months of planned randomization

Patients with CAD on DAPT