The use of metformin, a common regulator of blood glucose for diabetics, does not help protect against heart failure in non-diabetic patients who have suffered a heart attack, according to research presented at the American College of Cardiology’s 63rd Annual Scientific Session.

The GIPS-III trial is the first double-blind, randomized, placebo-controlled study conducted to evaluate whether four months of metformin treatment preserved left ventricular function in non-diabetic patients with acute myocardial infarction.

Metformin is commonly used in diabetic patients to control blood glucose levels by reducing the amount of glucose absorbed from food or made by the liver. Several observational studies suggested metformin has cardio-protective effects via mechanisms that are independent of the drug’s glucose-lowering effect.

Myocardial infarction often inflicts injury to the heart muscle, resulting in reduced left ventricular function and affecting the ability of the heart to pump blood throughout the body. Several studies in animal models of myocardial infarction showed that metformin preserved the ability of the heart to pump blood through the body (in other words, maintaining left ventricular function), leading researchers to speculate that the addition of metformin to the standard of care in heart attack patients could possibly prevent post-infarction heart failure.

“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 Chris P.H. Lexis, M.D., University Medical Center Groningen in the Netherlands, and lead investigator of the study.

“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.”

In this study, 380 patients who had acute myocardial infarction and underwent successful percutaneous coronary intervention were randomized to receive either 500 mg metformin twice daily or placebo in addition to standard of care according to the latest guidelines. The median age at baseline was 59. Patients with known diabetes or who needed coronary bypass surgery were excluded.

The primary endpoint was left ventricular ejection fraction, an accurate measure of left ventricular function, measured by MRI four months after infarction. The left ventricular ejection fraction in the metformin group was 53.1 percent compared to 54.8 percent in the placebo group, a difference that is not statistically significant.

The secondary endpoint was the level of N-terminal pro brain natriuretic peptide, which is considered a good indicator of cardiac dysfunction before it is detectable by MRI, at four months following percutaneous coronary intervention. N-terminal pro brain natriuretic peptide concentration was comparable between the groups at 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,” Lexis said.

The researchers say this is an example of how difficult it is to translate results of observational studies into an established treatment.

The results observed in the GIPS-III trial reflect metformin administration after PCI. Whether metformin given before percutaneous coronary intervention or even in a higher dose is of benefit remains to be explained.

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The GIPS-III trial, otherwise known as the Metabolic Modulation With Metformin to Reduce Heart Failure After Acute Myocardial Infarction Glycometabolic Interventions in Patients presenting with ST-elevation myocardial Infarction-III study, was funded by the Netherlands Organization for Health Research and Development.

This study will be simultaneously published online in the Journal of the American Medical Association at the time of presentation.

The ACC’s Annual Scientific Session brings together cardiologists and cardiovascular specialists from around the world each year to share the newest discoveries in treatment and prevention.
The American College of Cardiology is a nonprofit medical society comprised of 47,000 physicians, surgeons, nurses, physician assistants, pharmacists and practice managers. The College is dedicated to transforming cardiovascular care, improving heart health and advancing quality improvement, patient-centered care, payment innovation and professionalism. The ACC also leads the formulation of important cardiovascular health policy, standards and guidelines. It bestows credentials upon cardiovascular specialists, provides professional education, supports and disseminates cardiovascular research, and operates national registries to measure and promote quality care.

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Beth Casteel
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American College of Cardiology