• Chris P H Lexis, Iwan C C van der Horst, Erik Lipsic, Wouter G Wieringa, Rudolf A de Boer, Ad F M van den Heuvel, Hindrik W van der Werf, Remco A J Schurer, Gabija Pundziute, Eng S Tan, Wybe Nieuwland, Hendrik M Willemsen, Bernard Dorhout, Barbara H W Molmans, Anouk N A van der Horst-Schrivers, Bruce H R Wolffenbuttel, Gert J ter Horst, Albert C van Rossum, Jan G P Tijssen, Hans L Hillege, Bart J G L de Smet, Pim van der Harst, Dirk J van Veldhuisen, and GIPS-III Investigators.
• University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.
• JAMA. 2014 Apr 16;311(15):1526-35.

ImportanceMetformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function.ObjectiveTo evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI).Design, Setting, And ParticipantsDouble-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013.InterventionsMetformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months.Main Outcomes And MeasuresThe primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure.ResultsAt 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed.Conclusions And RelevanceAmong patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting.Trial Registrationclinicaltrials.gov Identifier: NCT01217307.

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