Effect of Metformin on Left Ventricular Function After Acute Myocardial Infarction in Patients Without Diabetes: The GIPS-III Randomized Clinical Trial

Study Questions:

What is the effect of metformin treatment on preservation of left ventricular (LV) function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI)?

Methods:

GIPS-III (Glycometabolic Intervention as Adjunct to Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction) was a double-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. Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months was administered. The primary efficacy measure was LV 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 endpoint of death, reinfarction, or target lesion revascularization) was recorded until 4 months as a secondary efficacy measure.

Results:

At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% confidence interval [CI], 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (p = 0.10) 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 = 0.66). MACE were observed in six patients (3.1%) in the metformin group and in two patients (1.1%) in the placebo group (p = 0.16). Creatinine concentration (79 μmol/L [IQR, 70-87 μmol/L] vs. 79 μmol/L [IQR, 72-89 μmol/L], p = 0.61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs. 5.9% [IQR, 5.7%-6.1%], p = 0.15) were not significantly different between both groups. No cases of lactic acidosis were observed.

Conclusions:

The authors concluded that among 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.

Perspective:

In this double-blind, randomized, controlled trial, in patients without diabetes who underwent primary PCI for STEMI, treatment with 500 mg of metformin administered twice daily for 4 months did not have an effect on LVEF or NT-proBNP levels, compared with placebo. Because LV function is currently regarded as the most important predictor of morbidity and mortality after STEMI, it is unlikely that metformin will have a significant effect on long-term outcome after STEMI in patients without diabetes. A role for metformin in preventing heart failure after MI remains unproven, and the present findings do not support the use of metformin in this setting.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Hemoglobin A, Glycosylated, Myocardial Infarction, Ventricular Function, Left, Metformin, Heart Failure, Peptide Fragments, Netherlands, Percutaneous Coronary Intervention, Natriuretic Peptide, Brain, ACC Annual Scientific Session


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