The Metformin in Coronary Artery Bypass Graft (CABG) (MetCAB) Trial

The Metformin in CABG (MetCAB) Trial

Rationale:

In patients with a myocardial infarction, occlusion of a coronary artery induces myocardial ischemia and cell death. If untreated, the area of myocardium exposed to this interruption in blood supply, will largely become necrotic. The only way to limit final infarct size, is timely reperfusion of the occluded artery. Paradoxically, however, reperfusion itself can also damage myocardial tissue and contribute to the final infarct size ("reperfusion injury"). Also during coronary artery bypass grafting (CABG), the myocardium is exposed to ischemia and reperfusion, which will induce cell death. Indeed, postoperatively, the plasma concentration of troponin I, a marker of cardiac necrosis, is increased, and associated with adverse outcome. The anti-hyperglycaemic drug metformin has been shown in preclinical studies to be able to reduce ischemia-reperfusion injury and to limit myocardial infarct size. Moreover, metformin therapy improves cardiovascular prognosis in patients with diabetes mellitus. Paradoxically, in patients with diabetes, current practice is to temporarily stop metformin before major surgery for the presumed risk of lactic acidosis, which is a rare complication of metformin. However, here is no evidence that this practice benefits the patient. The investigators hypothesize that pretreatment with metformin can reduce myocardial injury in patients undergoing elective CABG surgery

Inclusion Criteria:

• Acceptation for CABG with or without concomitant valve surgery
• Informed consent
• Age ≥ 18 years

Exclusion Criteria:

• Diabetes mellitus
• Renal dysfunction (MDRD < 60 ml/min)
• Elevated liver enzymes (ALAT > 3 times upper limit of reference range)
• Treatment with dipyridamole or xanthine derivatives
• Recent myocardial infarction (<2 weeks before inclusion)
• Off-pump surgery