Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis (TARGET Trial): Does Ticagrelor Improve Graft Patency After Coronary Bypass?

Conditions
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Saphenous Vein Graft Disease

Intervention / Treatment
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* Drug: Aspirin
* Drug: Ticagrelor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures Female and/or male patients aged 18-90 years Patients undergoing first-time CABG with at least 1 saphenous vein graft, irrespective of concurrent valve surgery Exclusion Criteria: Inability to provide informed consent Pregnancy or seeking pregnancy Patients undergoing redo-CABG Serum creatinine >1.8 mg/dL (need for contrast with CT coronary angiogram) Hypersensitivity or allergy to aspirin or ticagrelor Anticipated need for postoperative anticoagulation with coumadin, dabigatran or rivaroxaban (mechanical valve, chronic atrial fibrillation, DVT/PE) History of gastrointestinal hemorrhage Active pathological bleeding History of intracranial hemorrhage Severe hepatic impairment Current or anticipated use of strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, nefazadone, ritonavir, and atazanavir)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aspirin<br>One aspirin 81 mg capsule 2 times per day | Drug: Aspirin<br> <br> |
| Active Comparator: Ticagrelor<br>One ticagrelor 90 mg capsule 2 times per day | Drug: Ticagrelor<br> <br> * Other names: Brillinta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 1 year after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 1 year after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Saphenous vein graft disease, Coronary artery bypass graft surgery, Antiplatelet therapy, Coronary artery disease, Secondary prevention, Graft patency