Ticagrelor Antiplatelet Therapy to Reduce Graft Events and Thrombosis

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

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.

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.

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)