Aspirin Resistance in Coronary Artery Disease

Coronary Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00753935
• Other study ID #: 040065
• Secondary ID: 5P50HL081009-03
• Status: Completed
• Phase: Early Phase 1
• First received: September 15, 2008
• Last updated: March 19, 2018
• Start date: June 2006
• Est. completion date: March 2014

Study information

• Verified date: March 2018
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: March 2014
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• enteric-coated aspirin
enteric-coated aspirin 81mg daily for 2 weeks
• Chewable aspirin
chewable aspirin 81mg daily for 2 weeks

Locations

Country	Name	City	State
United States	Vanderbilt University	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Smith JP, Haddad EV, Taylor MB, Oram D, Blakemore D, Chen Q, Boutaud O, Oates JA. Suboptimal inhibition of platelet cyclooxygenase-1 by aspirin in metabolic syndrome. Hypertension. 2012 Mar;59(3):719-25. doi: 10.1161/HYPERTENSIONAHA.111.181404. Epub 2012 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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