Metformin 500 mg BID does not protect against heart failure after heart attack in non-diabetic patients

by Bruce Sylvester – Metformin therapy at 500 twice daily (BID) is not protective against heart failure in non-diabetic patients following a heart attack, researchers reported on March 31, 2014 at the American College of Cardiology’s 63rd Annual Scientific Session.

The findings were also simultaneously published online in the Journal of the American Medical Association (JAMA).

“This study did not prove the benefits of metformin in acute myocardial infarction and as such will not change clinical practice as we might have thought,” said lead investigator Chris P.H. Lexis, M.D., of the University Medical Center Groningen in the Netherlands. “However, it is noteworthy that metformin started early after heart attack did not adversely affect kidney function and was well-tolerated. So our findings do not preclude the use of metformin to treat diabetes in this setting.”

The GIPS-III (Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction Glycometabolic Interventions in Patients presenting with ST-elevation myocardial Infarction-III) trial was the first double-blind, randomized, placebo-controlled study to evaluate whether  metformin helped preserve left ventricular function in non-diabetic patients after acute myocardial infarction. Observational studies had suggested that metformin might be used as a cardio-protective agent in this clinical situation.

The investigators enrolled 380 subjects who had suffered acute myocardial infarction and had undergone successful percutaneous coronary intervention. They were randomized to 500 mg metformin BID or placebo, plus guideline-directed standard of care.

Median age at baseline was 59 years. Patients with diabetes or in need of coronary bypass surgery were ineligible for the study.

The primary endpoint was left ventricular ejection fraction function, measured by MRI four months after the heart attack.

The investigators reported that left ventricular ejection fraction in the metformin group was 53.1 percent compared to 54.8 percent in the placebo group, a statistically non-significant difference.

The secondary endpoint was the level of N-terminal pro brain natriuretic peptide, a signal of cardiac dysfunction before it can be spotted by MRI, at four months following percutaneous coronary intervention.

The investigators found that N-terminal pro brain natriuretic peptide concentration was similar between the groups, 167 ng/l in the metformin group and 167 ng/l in the placebo group.

“While this glucose-lowering drug is very effective in patients with diabetes and can be safely used in patients with a heart attack, [our data show] it is not of additional benefit in protecting the heart from damage resulting in decreased pump function of the heart,” Dr. Lexis added.

The GIPS-III trial was funded by the Netherlands Organization for Health Research and Development.