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WASHINGTON -- Metformin started soon after reperfusion in the acute setting didn't help cardiac function recover in non-diabetic heart attack patients, a trial showed.

with a 4-month course of the drug started immediately after percutaneous intervention for acute ST-segment myocardial infarction (STEMI) than with placebo (53% versus 55% of predicted, P=0.096).

N-terminal pro-brain natriuretic peptide (NT-proBNP) as a marker of cardiac stress came out at an identical 167 ng/L in both groups at that point, Chris Lexis, MD, of University Medical Center Groningen, the Netherlands, and colleagues found.

"The current results do not support use of metformin in this setting," Lexis concluded here at the American College of Cardiology meeting and simultaneously online in the Journal of the American Medical Association.

That wasn't surprising, , of NYU Langone Medical Center in New York City, told 乌鸦传媒.

"They gave this to a non-diabetic group," he said "So we're asking the question are there mystical properties, are there properties that beyond the range of what the drug is supposed to do, so-called pleiotropic properties that we've attributed with statins and ACE inhibitors and ARBs."

However, there was at least no signal of harm, , of the University of Texas Southwestern Medical Center in Dallas, noted in discussing the trial at a press conference.

There were no cases of severe renal impairment or lactic acidosis and no difference between groups in discontinuation for adverse events or elevations in laboratory markers of creatinine.

The only risk was the expected increase in nausea with the drug (10 cases versus 2, P=0.036).

"Metformin is one of the most common diabetes drugs," Khera said. "It does inform here at least that in patients with myocardial infarction it does seem to be safe giving metformin soon after."

The double-blind Glycometabolic Interventions in Patients presenting with STEMI ( included 380 STEMI patients randomized to 500 mg of metformin or placebo twice daily started immediately after percutaneous coronary intervention and continued for 4 months.

Among the secondary outcomes, no advantage was seen with metformin for the composite of death, reinfarction, or target lesion revascularization or its individual components.

Speculations on why the trial failed cited a number of possibilities.

One reason might just have been that there wasn't much room for improvement after reperfusion.

The ejection fractions were high overall in the trial due to the "incredible progress" made in STEMI care over the years, noted late-breaking clinical trial session co-chair , of the Cleveland Clinic.

"It's hard for them to do better," he said.

"Perhaps if they had come in later or with a larger amount of heart damage we could have seen an advantage, agreed Khera.

And if the presumed mechanism is preservation of left ventricular ejection fraction, it would have made more sense to give metformin before, not after PCI, added , of the University of California San Diego, and a discussant at the session.

However, there was no difference in impact of metformin by ischemic time, degree of ischemia before reperfusion, admission NT-proBNP, or admission glucose level.

The trial might have done better with a design that targeted higher-risk patients who stood to gain more, such as pre-diabetics, Weintraub suggested.

Patients found to be pre-diabetic during enrollment were started on medication without breaking blinding for metformin assignment, trial primary investigator Iwan van der Horst, MD, PhD, also of the University of Groningen, told 乌鸦传媒 Today.

A relatively high proportion (14% to 17%) of patients got diagnosed with diabetes by 4 months in the trial, which he chalked up to the fact that the trial looked for it and usual care doesn't.

No further trials in higher-risk populations or in different settings are planned at this time, van der Horst said.

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