Coronary Artery Disease
Conditions
Keywords
aspirin, aspirin resistance, aspirin nonresponse, cyclooxygenase, thromboxane, oxidative stress
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.
Interventions
enteric-coated aspirin 81mg daily for 2 weeks
DRUGChewable aspirin
chewable aspirin 81mg daily for 2 weeks
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enteric-coated Aspirin patients with coronary artery disease received enteric-coated aspirin 81 mg qd for 2 weeks | 45 |
| Chewable Aspirin Patients with coronary artery disease received chewable aspirin 81 mg qd for 2 weeks | 47 |
| Total | 92 |
Baseline characteristics
| Characteristic | Enteric-coated Aspirin | Total | Chewable Aspirin |
|---|---|---|---|
| Age, Continuous | 62 years | 65 years | 68 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 12 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 36 Participants | 78 Participants | 42 Participants |
| Region of Enrollment United States | 45 participants | 92 participants | 47 participants |
| Sex: Female, Male Female | 12 Participants | 26 Participants | 14 Participants |
| Sex: Female, Male Male | 33 Participants | 66 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 47 |
| other Total, other adverse events | 0 / 45 | 0 / 47 |
| serious Total, serious adverse events | 0 / 45 | 0 / 47 |
Outcome results
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.
Time frame: after 2 weeks on aspirin
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enteric-coated Aspirin | Change in Serum Thromboxane B2 | 5.02 ng/mL |
| Chewable Aspirin | Change in Serum Thromboxane B2 | 2.78 ng/mL |
p-value: 0.005Wilcoxon rank-sum