Comparing High and lOw-dose asPirin With Dual anTIplatelet Therapy for Three Months Using prasUgrel and aSpirin Following Coronary Artery Bypass Grafting. (OPTIMUS-CABG Trial)

This is a multicenter, randomized trial evaluating the effect of low-dose aspirin plus prasugrel versus low-dose ASA and versus high-dose ASA for three months, followed by low-dose ASA alone, on graft failure at 12 months in patients with stable coronary artery disease (chronic coronary syndrome) following a coronary artery bypass grafting.

Inclusion criteria

A. Baseline (preoperative) inclusion criteria

• Age >18 years
• Primary isolated CABG patients with stable coronary artery disease (chronic coronary syndrome) planned for at least 2 grafts. Coronary artery disease will be defined as a stenosis ≥ 70% based on coronary angiography, a FFR value ≤ 0.80 or iFr value ≤0.89; a left main diameter stenosis ≥ 50%, left main IVUS MLA value ≤ 6 mm2, or equivalent OCT measurements will also be considered.
• Ability to comply with all study procedures and follow-up procedures
• Signed Informed Consent to participate in the study.

B. Operative inclusion criteria:

• Intraoperative graft evaluation using transit time flow measurement in all grafts, normal flow in any graft is defined as mean graft flow > 15 mL/min with Pulsatility Index < 5
• Left anterior descending artery grafted with internal thoracic artery
• No intraoperative decision for hybrid revascularization due to incomplete revascularization (Percutaneous coronary intervention (PCI) of the ungrafted vessel)
• No endarterectomy of the grafted vessel performed
• Patient did not have any additional unplanned procedure (Ex. LAAC, Ablation, valve intervention, aortic intervention)

Exclusion criteria

A. Baseline (preoperative) exclusion criteria:

• Cardiogenic shock
• Patients with recent acute coronary syndrome (ACS) (<12 months)
• Single vessel CABG
• Patients with preoperative atrial fibrillation
• Dialysis
• Thrombocytopenia (platelet count < 100 000 platelets/uL)
• Anemia (Hemoglobin level < 10 g/dL)
• Severe liver failure Child-Pugh classification >4
• Known, active infections with HIV, HBV, HCV, tuberculosis
• Active malignant disease or history of malignancy within the past 5 years
• Indication for DAPT (e.g. recent PCI or ACS or recent stents of peripheral arteries)
• Indication for oral anticoagulant treatment 13 Indications for the use of methotrexate at a dose of 15 mg/week or more

• Any contraindication for prasugrel or ASA 15. Planned additional cardiac or non-cardiac surgery within 12 months 16. Non-cardiac co-morbidity with life expectancy less than 12 months 17. History of any bleeding complications due to the use of DAPT 18. History of intracranial bleeding 19. History of gastro-intestinal bleeding 20. Pregnancy or breastfeeding 21. Lack of compliance with the use of a highly effective method of birth control 22. Planned coronary endarterectomy 23. Severe impaired renal function (eGFR <40mL/min/1.73 m2).

B. Postoperative and prior randomization exclusion criteria:

• Perioperative cardiogenic shock
• Intraoperative death or death prior randomization
• Myocardial infarction within 12-24 hours following CABG or prior randomization
• Ischemic or hemorrhagic stroke within 12-24 hours following CABG or prior randomization
• Any postoperative complication that may increase patients' risk with DAPT
• Atrial Fibrillation prior randomization
• Gastro-intestinal bleeding prior randomization