Coronary Artery Disease, Type 2 Diabetes Mellitus
Conditions
Keywords
diabetes mellitus, coronary artery disease, aspirin therapy
Brief summary
Since diabetic platelets are characterized by an enhanced turnover rate, it may be hypothesized that an increase in the frequency, rather than the dose, of drug administration may be a more effective strategy to inhibit platelet reactivity in diabetic patients as this may enable COX-1 blockade of newly generated platelets. However, how different dosing regimens impact the pharmacodynamic effects of aspirin selectively in diabetes mellitus has been poorly explored. Therefore, the aim of the present pilot investigation was to evaluate how increasing the frequency of aspirin administration, remaining within the daily recommended therapeutic doses, affects antiplatelet responsiveness in diabetic patients with coronary artery disease.
Interventions
DRUGAspirin
After having been on aspirin 81mg/daily for at least one-week, patients switched their aspirin regimen on a weekly basis according to the following scheme: aspirin 81mg twice daily (bid) for one week; aspirin 162 mg once daily (od) for one week; aspirin 162 mg bid for one week; aspirin 325 mg od for one week. Pharmacodynamic assessments were made after each sequence (5 time-points). Afterward, patients resumed the dose of aspirin that they were on prior to entering the study.
Sponsors
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Medically treated (taking oral hypoglycemic medication and/or insulin) type 2 diabetes mellitus patients between 18 to 75 years with stable coronary artery disease
Exclusion criteria
* Blood dyscrasia or bleeding diathesis * Oral anticoagulation therapy with a coumadin derivative * Recent antiplatelet treatment (\< 30 days) with a glycoprotein IIb/IIIa antagonist, thienopyridine (ticlopidine, clopidogrel), cilostazol or dipyridamole Platelet count \< 100 /microL * History of gastrointestinal bleed within last 6 months * History of cerebrovascular accident within last 3 months * History of hospitalization for an acute coronary event or coronary revascularization (percutaneous or surgical) in the past 12 months * Active bleeding or hemodynamic instability * Any active malignancy * Serum creatinine \> 2 mg/dL * Baseline ALT \> 2.5 times the upper limit of normal * Pregnant females * HbA1C \> 10% * Use of nonsteroidal anti-inflammatory drugs past 10 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Collagen Induced Aggregation | after 1 -week of treatment | Collagen induced aggregation using light transmittance aggregometry |
Countries
United States
Participant flow
Recruitment details
From January 2009 to April 2010 patients were recruited at the outpatient clinic of the Division of Cardiology at Shands Jacksonville Hospital.
Pre-assignment details
A total of 82 patients were screened; 48 were eligible and 36 agreed to provide their written consent. Of these, 16 did not complete all 5 treatment regimens. Therefore, a total of 20 completed all the study phases and used for analysis.
Participants by arm
| Arm | Count |
|---|---|
| Aspirin Dose Range Patients with type 2 DM on aspirin therapy will undergo treatment with escalating aspirin doses. Patients modified their aspirin regimen on a weekly basis according to the following scheme: 81mg/od. 81mg/bid, 162 mg/od, 162 mg/bid, 325mg/od. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 16 |
Baseline characteristics
| Characteristic | Aspirin Dose Range |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants |
| Age Continuous | 59 years STANDARD_DEVIATION 7 |
| Region of Enrollment United States | 36 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Collagen Induced Aggregation
Collagen induced aggregation using light transmittance aggregometry
Time frame: after 1 -week of treatment
Population: A 20% SD for the difference between collagen-induced platelet aggregation in patients on aspirin 81 mg od versus 81 mg bid was assumed, and based on a power of 80% and a significance level of 0.05. Based on these values, we determined that a sample population of 20 patients would be needed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aspirin Dose Range | Collagen Induced Aggregation | 32 percentage of platelet aggregation | Standard Deviation 14 |