The RATIO Study is a multicenter, nationwide, randomized, controlled, single blinded, unfunded trial of n. 900 patients undergoing multivessel OPCAB (≥2 grafts). This study is designed to test in patients undergoing off-pump coronary artery bypass surgery the hypothesis that full (high dose, 300 U/kg) and half (low dose,150 U/kg) heparinization are not different in terms of thrombotic complications and major perioperative bleeding events (null hypothesis).

Off-pump coronary artery bypass grafting (OPCAB) is an established alternative to on-pump coronary artery bypass grafting (CABG). OPCAB determines a pro-coagulant state potentially deleterious on grafts patency, that is not counterbalanced by the adverse effects of cardiopulmonary bypass on coagulation occurring in CABG, and that lasts as long as one month. Therefore in OPCAB systemic heparinization is necessary to prevent thrombotic complications during transitory occlusion of coronary arteries and grafts. An internationally accepted standard intra-operative anticoagulation protocol for OPCAB has not yet been defined, and heparinization in OPCAB is a highly variable practice. The intraoperative anticoagulation regimen adopted in patients undergoing OPCAB may influence major postoperative outcomes, such as bleeding, transfusion requirements, inflammatory response, myocardial ischemia and grafts patency, but it has never been the object of large-scale randomized controlled trial (RCT). The 2 most widespread intraoperative anticoagulation protocols in OPCAB are represented by full (300 U/kg) or half (150 U/kg) heparinization, with target ACT ranging from 200 sec to >480 sec.

Patients enrolled in the study will be randomized to receive full or half heparinization in a 1:1 ratio using a randomization schedule blocked by site. Randomization will take place in the operatory room by the anesthesiologist, and will be blinded to the surgeon.

Inclusion Criteria:

Consecutive patients electively undergoing multivessel OPCAB

Exclusion Criteria:

Acute coronary syndrome, on-going double anti-platelets treatment (the second antiplatelet drug should be suspended 5 days before surgery), on-going intravenous heparin or sub-cutaneous low molecular weight heparin, known coagulopathy, documented liver disease, chronic renal failure (creatinine ≥ 2 mg/dl) or previous renal transplantation surgery, previous cardiac surgery.