Metformin doesn't improve LVF after MI in non-diabetic patients

By Anne Harding

NEW YORK (Reuters Health) - Giving metformin to non-diabetics after an acute myocardial infarction does not improve left ventricular function, a new randomized trial shows.

"The study anticipated at least a difference of 3% in left ventricular ejection fraction in favor of patients on metformin," Dr. Iwan C. C. van der Horst of University Medical Center Groningen in the Netherlands, principal investigator on the GIPS-III study, told Reuters Health via email. "This result was not observed."

Diabetics on metformin have improved survival after ST-segment elevation MI (STEMI), while studies in animals suggest the drug may help preserve left ventricular function when given before and during ischemia-reperfusion, Dr. van der Horst and colleagues note in their report. To investigate whether metformin might improve left ventricular function in patients without diabetes, the investigators randomly assigned 380 non-diabetic patients who underwent PCI for STEMI at their center to receive 500 mg of metformin or placebo twice a day for four months.

At four months, all patients were still alive. Left ventricular ejection fraction (LVEF) was 53.1% in patients who received metformin, and 54.8% in those on placebo (p=0.10).

Secondary efficacy measures, including concentration of N-terminal pro-brain natriuretic peptide and incidence of major adverse cardiac events, were also similar in the two groups.

There were no significant differences between the two groups in creatinine concentration or glycated hemoglobin, and none of the patients developed lactic acidosis.

One possible explanation for the lack of an effect of metformin could have been that it took an average of four hours after PCI for the drug to reach effective plasma levels, Dr. van der Horst and his team note. "The role of metformin started earlier and in higher dose than in the GIPS-III remains to be elucidated," he said in an interview.

Dr. John Calvert, an assistant professor in the Department of Surgery at Emory School of Medicine in Atlanta, reviewed the new study for Reuters Health. "We did some of the critical preclinical animal studies, and we found that you had to have the metformin on board very soon after we perfused the artery," Dr. Calvert noted. In future clinical trials, he added, it might be effective to test giving patients a liquid form of metformin while PCI is being done.

Dr. Calvert said his own research shows that metformin affects cytoprotective pathways through AMP-activated protein kinase, and improves nitric oxide bioavailability.

"They did a good job with the study and I think the patient population they chose was pretty good, because these patients aren't really in severe heart failure, so you would hope if you did see improvement you would have seen it in these guys," Dr. Calvert said.

"I think the data with the diabetic patients is promising," he added, "and that is a patient population that is more at risk of developing a heart attack, so I think there is a clinical use of metformin for those patients."

The study was reported online March 31 in the Journal of the American Medical Association, to coincide with a presentation at the annual meeting of the American College of Cardiology.

SOURCE: http://bit.ly/1hoVtvS

JAMA 2014.

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