Aspirin Resistance in Coronary Artery Disease

Aspirin is commonly used for its antithrombotic effects in patients at risk for
cardiovascular events. Its primary mechanism of action is the irreversible acetylation of
platelet cyclooxygenase-1, thereby inhibiting platelet production of thromboxane A2, a potent
vasoconstrictor and activator of platelets. Thromboxane A2, the major product of
cyclooxygenase cytochrome oxidase (COX-1) in platelets, induces platelet aggregation.
Thromboxane B2 is an inactive metabolite/product of thromboxane A2. This primary outcome
measures the extent of inhibition of platelet COX-1 by measuring the amount of the metabolite
thromboxane B2 in serum.

Previous studies have demonstrated that many patients have recurrent events despite treatment
with aspirin, which has been termed "aspirin resistance" or "aspirin nonresponse." This study
addresses some of the possible mechanisms for aspirin nonresponse; specifically, we will test
the hypothesis that aspirin nonresponse results from states that produce high peroxide
concentrations ("oxidative stress") in platelets. In addition, we will evaluate the effect of
enteric coating on the pharmacologic efficacy of aspirin in patients with coronary artery
disease.

Inclusion Criteria:

- On aspirin 81-325mg daily at time of enrollment

- Documented stable coronary artery disease or > 6 months after coronary artery bypass
grafting or interventional cardiac procedure

- Written informed consent

Exclusion Criteria:

- Pre-menopausal female

- Renal disease (creatinine >= 2 mg/dl)

- Anemia (Hematocrit < 30%)

- Thrombocytopenia (platelet count < 135,000/ul)

- Use of NSAIDs or coxibs within the previous 2 weeks

- Concurrent use of other anti-platelet agents

- Uncontrolled hypertension (systolic BP > 180 mmHg)

- Decompensated congestive heart failure

- Recent coronary syndrome (< 6 months)

- History of significant GI bleeding