Aspirin Resistance in Coronary Artery Disease

Early Phase 1

Completed

• Conditions: Coronary Artery Disease
• Interventions: Drug: enteric-coated aspirin; Drug: Chewable aspirin

• Registration Number: NCT00753935
• Lead Sponsor: Vanderbilt University

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.

Study Timeline

• Study Start: 2006-06
• Study First Submitted: 2008-09-15
• Study First Submitted QC: 2008-09-15
• Study First Posted: 2008-09-17
• Primary Completion: 2011-08
• Study Completion: 2014-03
• Results First Submitted: 2017-04-07
• Status Verified: 2018-03
• Results First Submitted QC: 2018-03-19
• Last Update Submitted: 2018-03-19
• Results First Posted: 2018-04-19
• Last Update Posted: 2018-04-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 92

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Enteric-coated aspirin	enteric-coated aspirin	patients received enteric-coated aspirin 81 mg qd for 2 weeks
Chewable aspirin	Chewable aspirin	Patients received chewable aspirin 81 mg qd for 2 weeks

Primary Outcome Measures

Name	Time	Method
Change in Serum Thromboxane B2	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.

Trial Locations

Locations (1)

Vanderbilt University; 🇺🇸 Nashville, Tennessee, United States