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