Saphenous Vein Graft Disease
Conditions
Keywords
Saphenous vein graft disease, Coronary artery bypass graft surgery, Antiplatelet therapy, Coronary artery disease, Secondary prevention, Graft patency
Brief summary
Saphenous vein graft disease remains an unresolved medical problem. Many vein grafts occlude in the first year after bypass surgery, leading to adverse cardiovascular outcomes, including recurrent angina, myocardial infarction, and the need for repeat coronary intervention. While aspirin is the standard antiplatelet treatment after CABG surgery, 10-20% of vein grafts continue to occlude despite contemporary secondary preventative therapy. Compared to aspirin and other antiplatelet therapies like clopidogrel, ticagrelor treatment leads to a more pronounced platelet inhibition, and may substantially improve graft patency following CABG compared to aspirin. No data has yet to be collected regarding the impact of ticagrelor on saphenous vein graft patency following CABG. In this context, the investigators seek to compare vein graft patency between patients randomized to receive aspirin therapy, the current standard of care, or ticagrelor treatment, starting in the early postoperative period, and continuing for 2 years after CABG.
Detailed description
This clinical trial will be a randomized double-blind study focusing on ticagrelor antiplatelet therapy as a means of improving vein graft patency after CABG. Patients will be eligible if they have received at least 1 vein bypass graft at time of surgery. Patients will be randomized to receive either aspirin 81 mg bid or ticagrelor 90 mg bid. The aspirin and ticagrelor medications will be prepared in blinded capsules. Patients recovering from surgery will be eligible for study randomization within the first 5 postoperative days. Treatment will continue for 1 year, at which time patients will undergo a CT coronary angiogram to assess graft patency. Patients will then be invited to continue participating in the trial for 1 more year, and a repeat CT coronary angiogram will be performed at the 2 year postoperative time-point.
Interventions
DRUGAspirin
DRUGTicagrelor
Sponsors
AstraZeneca
Ottawa Heart Institute Research Corporation
Boca Raton Regional Hospital
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 90 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of informed consent prior to any study specific procedures 2. Female and/or male patients aged 18-90 years 3. Patients undergoing first-time CABG with at least 1 saphenous vein graft, irrespective of concurrent valve surgery
Exclusion criteria
1. Inability to provide informed consent 2. Pregnancy or seeking pregnancy 3. Patients undergoing redo-CABG 4. Serum creatinine \>1.8 mg/dL (need for contrast with CT coronary angiogram) 5. Hypersensitivity or allergy to aspirin or ticagrelor 6. Anticipated need for postoperative anticoagulation with coumadin, dabigatran or rivaroxaban (mechanical valve, chronic atrial fibrillation, DVT/PE) 7. History of gastrointestinal hemorrhage 8. Active pathological bleeding 9. History of intracranial hemorrhage 10. Severe hepatic impairment 11. Current or anticipated use of strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, nefazadone, ritonavir, and atazanavir)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Saphenous Vein Graft Occlusion | 1 year after surgery | The primary objective of this clinical trial will be to evaluate whether, as compared to usual aspirin treatment, ticagrelor early after CABG prevents saphenous vein graft occlusion 1 year after surgery, as assessed by computed tomography (CT) coronary angiography. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Saphenous Vein Graft Stenosis | 1 year after surgery | The secondary objective of this clinical trial will be to evaluate whether, as compared to usual aspirin treatment, ticagrelor early after CABG prevents saphenous vein graft stenosis, defined as \>50% narrowing of the graft, 1 year after surgery, as assessed by computed tomography (CT) coronary angiography. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aspirin aspirin group | 123 |
| Ticagrelor ticagrelor group | 127 |
| Total | 250 |
Baseline characteristics
| Characteristic | Aspirin | Ticagrelor | Total |
|---|---|---|---|
| Age, Continuous | 68.0 years STANDARD_DEVIATION 9 | 67.5 years STANDARD_DEVIATION 9.3 | 68.0 years STANDARD_DEVIATION 9 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 16 Participants | 23 Participants | 39 Participants |
| Sex: Female, Male Male | 107 Participants | 104 Participants | 211 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 123 | 2 / 127 |
| other Total, other adverse events | 0 / 123 | 0 / 127 |
| serious Total, serious adverse events | 5 / 123 | 9 / 127 |
Outcome results
Primary
Saphenous Vein Graft Occlusion
The primary objective of this clinical trial will be to evaluate whether, as compared to usual aspirin treatment, ticagrelor early after CABG prevents saphenous vein graft occlusion 1 year after surgery, as assessed by computed tomography (CT) coronary angiography.
Time frame: 1 year after surgery
Population: Vein graft occlusion reported as percentage
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | Saphenous Vein Graft Occlusion | 17.4 percentage of veins occluded |
| Ticagrelor | Saphenous Vein Graft Occlusion | 13.2 percentage of veins occluded |
Secondary
Saphenous Vein Graft Stenosis
The secondary objective of this clinical trial will be to evaluate whether, as compared to usual aspirin treatment, ticagrelor early after CABG prevents saphenous vein graft stenosis, defined as \>50% narrowing of the graft, 1 year after surgery, as assessed by computed tomography (CT) coronary angiography.
Time frame: 1 year after surgery
Population: Vein graft stenosis reported as percentage
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin | Saphenous Vein Graft Stenosis | 4.1 percentage of veins stenosed |
| Ticagrelor | Saphenous Vein Graft Stenosis | 4.2 percentage of veins stenosed |