Aspirin Resistance in Coronary Artery Disease

Study 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.

Official Title
-----------------
Evaluation of Aspirin Resistance at a Molecular Level in Aspirin-Treated Patients With Coronary Artery Disease

Conditions
-----------------
Coronary Artery Disease

Intervention / Treatment
-----------------
* Drug: enteric-coated aspirin
* Drug: Chewable aspirin


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enteric-coated aspirin<br>patients received enteric-coated aspirin 81 mg qd for 2 weeks | Drug: enteric-coated aspirin<br>* enteric-coated aspirin 81mg daily for 2 weeks<br>* Other names: acetylsalicylic acid;|
| Active Comparator: Chewable aspirin<br>Patients received chewable aspirin 81 mg qd for 2 weeks | Drug: Chewable aspirin<br>* chewable aspirin 81mg daily for 2 weeks<br>* Other names: acetylsalicylic acid;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Thromboxane B2 | 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. | after 2 weeks on aspirin | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
aspirin, aspirin resistance, aspirin nonresponse, cyclooxygenase, thromboxane, oxidative stress