Evaluation of Aspirin Resistance at a Molecular Level in Aspirin-Treated Patients With Coronary Artery Disease
Overview
- Phase
- Early Phase 1
- Intervention
- Chewable aspirin
- Conditions
- Coronary Artery Disease
- Sponsor
- Vanderbilt University
- Enrollment
- 92
- Locations
- 1
- Primary Endpoint
- Change in Serum Thromboxane B2
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The purpose of this study is to evaluate possible mechanisms of aspirin resistance at a molecular level in aspirin-treated patients with coronary artery disease. We hypothesize that certain patient characteristics associate with aspirin resistance. In addition, we will compare the effects of enteric-coated aspirin and chewable aspirin.
Detailed Description
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.
Investigators
John Oates
Professor of Medicine and Pharmacology
Vanderbilt University
Eligibility Criteria
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
Arms & Interventions
Chewable aspirin
Patients received chewable aspirin 81 mg qd for 2 weeks
Intervention: Chewable aspirin
Enteric-coated aspirin
patients received enteric-coated aspirin 81 mg qd for 2 weeks
Intervention: enteric-coated aspirin
Outcomes
Primary Outcomes
Change in Serum Thromboxane B2
Time Frame: after 2 weeks on aspirin
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.