Atherosclerosis
Conditions
Keywords
Saphenous vein, Intimal hyperplasia, Coronary artery bypass graft surgery, Antiplatelet therapy, Clopidogrel, Saphenous vein graft disease
Brief summary
The purpose of this study is to determine whether the combination of clopidogrel with aspirin prevents the development of blockages (atherosclerosis) in vein grafts one year after coronary artery bypass surgery (CABG) compared to aspirin alone.
Detailed description
Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery (CABG). The process of saphenous vein intimal hyperplasia is mediated by platelet aggregation and begins just days after surgical revascularization. Subsequently, areas of intimal hyperplasia in turn develop graft atherosclerotic disease and its sequelae. Clopidogrel improves outcomes in patients with atherosclerotic disease, and is effective at reducing intimal hyperplasia in animal models of thrombosis. Therefore, the goal of this study will be to evaluate the efficacy of clopidogrel and aspirin therapy versus aspirin alone in the prevention of saphenous vein graft intimal hyperplasia following one year after CABG. Patients undergoing multi-vessel CABG and in whom at least two saphenous vein grafts will be used are eligible for the study. Patients will be randomized to receive daily clopidogrel 75 mg or placebo, in addition to daily aspirin 162 mg, for the duration of one year starting as soon as postoperative bleeding has been ruled out on the day of surgery. At the end of one year, all patients will undergo coronary angiography and intravascular ultrasound assessment of one saphenous vein graft as selected by randomization. The study will be powered to test the hypothesis that clopidogrel and aspirin will reduce vein graft intimal hyperplasia by 20% compared to aspirin alone at one year following bypass surgery.
Interventions
Daily dose of 75 mg Clopidogrel
DRUGwater pill daily
Daily dose of water pill (placebo)
Sponsors
Sanofi
Bristol-Myers Squibb
Ottawa Heart Institute Research Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients undergoing primary multi-vessel CABG with at least two saphenous vein grafts, with or without the use of cardiopulmonary bypass.
Exclusion criteria
* Emergency surgery * Valve surgery * Redo CABG * Left ventricle ejection fraction \< 25% * Serum creatinine \> 130 µmol/L * Preoperative use of clopidogrel (with the exception of the current admission) * Preoperative use of warfarin; allergy to aspirin or clopidogrel. * History of cerebrovascular accident * History of severe liver disease * Morbid obesity * Current malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vein Graft Intimal Area | One year following surgery | IVUS imaging 12 months post-CABG, and the average intimal area in the proximal 40 mm of one vein graft per patient will be assessed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vein Graft Angiographic Patency | One year following surgery | Postoperative angiogram 12 months post-CABG |
| Incidence of Major Adverse Coronary Events Within One Year Following Surgery | 1 year | — |
| Incidence of Major Bleeding Events Within One Year Following Surgery | 1 year | — |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 75mg Clopidogrel 75mg clopidogrel. 162mg ASA is also given, but is a standard-of-care post operative to cardiac surgery.
Clopidogrel 75 mg daily: Daily dose of 75 mg Clopidogrel | 56 |
| Placebo Water pill. 162mg ASA is also given, but is a standard-of-care post operative to cardiac surgery.
water pill daily: Daily dose of water pill (placebo) | 57 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 5 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 3 |
| Overall Study | Withdrawal by Subject | 7 | 3 |
Baseline characteristics
| Characteristic | 75mg Clopidogrel | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 64.9 years STANDARD_DEVIATION 7.5 | 68.1 years STANDARD_DEVIATION 7.4 | 66.0 years STANDARD_DEVIATION 7.4 |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 51 Participants | 50 Participants | 101 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 1 / 57 |
| other Total, other adverse events | 3 / 56 | 3 / 57 |
| serious Total, serious adverse events | 4 / 56 | 5 / 57 |
Outcome results
Primary
Vein Graft Intimal Area
IVUS imaging 12 months post-CABG, and the average intimal area in the proximal 40 mm of one vein graft per patient will be assessed
Time frame: One year following surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 75mg Clopidogrel | Vein Graft Intimal Area | 4.1 mm | Standard Deviation 2 |
| Placebo | Vein Graft Intimal Area | 4.5 mm | Standard Deviation 2.1 |
Secondary
Incidence of Major Adverse Coronary Events Within One Year Following Surgery
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 75mg Clopidogrel | Incidence of Major Adverse Coronary Events Within One Year Following Surgery | 4 Participants |
| Placebo | Incidence of Major Adverse Coronary Events Within One Year Following Surgery | 5 Participants |
Secondary
Incidence of Major Bleeding Events Within One Year Following Surgery
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 75mg Clopidogrel | Incidence of Major Bleeding Events Within One Year Following Surgery | 1 Participants |
| Placebo | Incidence of Major Bleeding Events Within One Year Following Surgery | 0 Participants |
Secondary
Vein Graft Angiographic Patency
Postoperative angiogram 12 months post-CABG
Time frame: One year following surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 75mg Clopidogrel | Vein Graft Angiographic Patency | 94.3 percentage |
| Placebo | Vein Graft Angiographic Patency | 93.2 percentage |