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

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

El Messaoudi S, Nederlof R, Zuurbier CJ, van Swieten HA, Pickkers P, Noyez L, Dieker HJ, Coenen MJ, Donders AR, Vos A, Rongen GA, Riksen NP. Effect of metformin pretreatment on myocardial injury during coronary artery bypass surgery in patients without diabetes (MetCAB): a double-blind, randomised controlled trial. Lancet Diabetes Endocrinol. 2015 Aug;3(8):615-23. doi: 10.1016/S2213-8587(15)00121-7. Epub 2015 Jul 12.

Riksen NP, el Messaoudi S, Rongen GA. It takes more than one CAMERA to study cardiovascular protection by metformin. Lancet Diabetes Endocrinol. 2014 Feb;2(2):105-6. doi: 10.1016/S2213-8587(13)70207-9. Epub 2014 Feb 3. No abstract available.