Clinical trial NCT00753935: Aspirin Resistance in Coronary Artery Disease
Official title: Evaluation of Aspirin Resistance at a Molecular Level in Aspirin-Treated Patients With Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Coronary Artery Disease
Keywords: aspirin
aspirin resistance
aspirin nonresponse
cyclooxygenase
thromboxane
oxidative stress
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2008-09-17
Enrollment: 92
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Change in Serum Thromboxane B2
timeFrame: after 2 weeks on aspirin
Secondary outcomes:
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Mary B Taylor, MD, MSCI
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 Feb 6.