Treatment with metformin failed to show any positive effects on left ventricular function in diabetes-free patients who presented with ST-segment elevation MI, according to the results of a double-blind, placebo-controlled study.
The study in 380 patients undergoing primary percutaneous coronary intervention – 191 of whom were given metformin and 189 of whom were given placebo – found no significant effects of twice-daily metformin (500 mg) on left ventricular ejection fraction (LVEF) after 4 months of treatment, and there was no significant difference in the incidence of major cardiac events between the two groups, Dr. Chris P. H. Lexis said at the annual meeting of the American College of Cardiology.
Dr. Chris P.H. Lexis
Specifically, at 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% in the metformin group, compared with 54.8% in the placebo group. NT-proBNP concentration was 167 ng/L in the metformin group and 167 ng/L in the placebo group. Major adverse cardiovascular events were observed in six patients (3.1%) in the metformin group and in two patients (1.1%) in the placebo group. Creatinine concentration (79 micromol/L vs. 79 micromol/L) and glycated hemoglobin (5.9% vs. 5.9%) were not significantly different between both groups. No cases of lactic acidosis were observed, according to the investigators.
Up to half of patients who experience an ST-segment elevation MI (STEMI) develop left ventricular dysfunction, which is the strongest predictor of adverse outcomes, such as heart failure.
Findings from previous animal studies had suggested that metformin may have favorable effects on ventricular function, possibly through enhanced phosphorylation of AMP-activated protein kinase causing changes in intracellular pathways and altering mitochondrial function, in turn resulting in improved systolic and diastolic function.
"Data from experimental studies have suggested that administration of metformin before and during ischemia reperfusion might affect these protective pathways and preserve left ventricular function, independent of glycometabolic state," according to Dr. Lexis of the University of Groningen, the Netherlands, and his associates, in a paper simultaneously published online in JAMA (2014 March 31 [doi:10.1001/jama.2014.3315]).
"Moreover, in observational studies of patients with acute myocardial infarction, concurrent treatment with metformin was associated with lower peak values of CK [creatine kinase], myocardial band of CK, and troponins and with improved survival after STEMI in patients with type 2 diabetes, compared with other antihyperglycemic strategies."