Evaluation of Aspirin Resistance at a Molecular Level in Aspirin-Treated Patients With Coronary Artery Disease
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Change in Serum Thromboxane B2
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Chewable aspirin
Patients received chewable aspirin 81 mg qd for 2 weeks
干预措施: Chewable aspirin (Drug)
Enteric-coated aspirin
patients received enteric-coated aspirin 81 mg qd for 2 weeks
干预措施: enteric-coated aspirin (Drug)
结局指标
主要结局
Change in Serum Thromboxane B2
时间窗: 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.
次要结局
未报告次要终点
研究者
John Oates
Professor of Medicine and Pharmacology
Vanderbilt University