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BARCELONA -- Starting patients on empagliflozin (Jardiance) in the acute phase of a large myocardial infarction (MI) resulted in improvements in surrogate markers of heart failure (HF) and heart function over the next half year, according to EMMY trial results presented here.

In this study, NT-proBNP levels at 6 months were reduced by 15% between people randomized to empagliflozin or placebo within 72 hours of percutaneous coronary intervention (PCI; P=0.026), a finding accompanied by significant improvement in left ventricular ejection fraction (LVEF) and other echocardiographic functional and structural parameters.

In fact, LVEF curves separated early such that the magnitude of improvement with the SGLT2 inhibitor was already approximately twice that of placebo (+8.8% vs +4.3%) by 6 weeks, reported Harald Sourij, MD, of Medical University of Graz in Austria, at the . A full report was simultaneously published in .

Empagliflozin was not associated with excess serious adverse events, and there was no signal of increased renal injury or symptomatic hypoglycemia.

These results boost optimism that SGLT2 inhibitors may provide clinical benefits post-MI, according to an by Javed Butler, MD, MPH, of Baylor Scott and White Research Institute in Dallas, and two colleagues.

"The need for new therapies in the post-MI population to mitigate risk of HF and mortality is a pressing one. It has been estimated that 12-15% of patients with MI will be hospitalized with HF in the year following their MI, and the presence of HF symptoms at time of MI has been identified as the single most powerful predictor of mortality," the editorialists said.

The EMMY data follow in the heels of the DELIVER presentation, also at ESC, that had cardiologists convinced that SGLT2 inhibitors can help clinical outcomes in heart failure across the spectrum of ejection fraction.

With people with recent ischemic events having been excluded from the major trials of SGLT2 inhibitors, however, it cannot be assumed that SGLT2 inhibitors will benefit the immediate post-MI population.

Butler and colleagues cited sacubitril-valsartan (Entresto) as an example of a drug that has proven efficacy in chronic HF but not in the post-MI setting.

Ultimately, Sourij said the "holy grail" would be to understand how SGLT2 inhibitors really work, as different mechanisms have been proposed. "It's important to understand how the drugs work exactly, then understand when to start [them]," he told the audience.

This class of medication was originally developed as diabetes drugs that lower blood sugar. By orders of the FDA to monitor their cardiovascular safety, they were subsequently and surprisingly shown to work for heart failure.

EMMY was conducted as a multicenter, double-blind trial in Austria. Participants were 476 adults with large acute MI accompanied by a large creatine kinase elevation. Those already using SGLT2 inhibitors were excluded

Participants were randomized to empagliflozin 10 mg or matching placebo once daily soon after PCI.

All together, the patients had a median age of 57 years, with 18% being women. There were 13% with established type 2 diabetes at baseline. Median NT-proBNP was 1,294 pg/ml.

During the course of the study, seven patients were hospitalised for heart failure (three in the empagliflozin group). Three deaths occurred, all among empagliflozin users.

"Two participants died within 5 days after enrolment in the trial secondary to large MIs and subsequent cardiogenic shock. One participant died 149 days after enrolment due to lung cancer. All three fatalities were considered by the adjudication committee prior to unblinding to be unrelated to study medication," Sourij and colleagues wrote.

The separation of the curves observed in EMMY prompted ESC session co-moderator Felicita Andreotti, MD, PhD, of IRCCS Foundation Agostino Gemelli University Hospital in Rome, Italy, to suggest longer follow-up in the trial.

Sourij acknowledged that there are no plans for further follow-up of this cohort.

Other limitations of EMMY include the reliance on surrogate markers and a sample too small to assess potential differences in actual clinical events between groups, according to Butler's group.

"Given the relatively low-risk population that was enrolled in EMMY trial, it may also be possible that these benefits will extend to relatively lower risk post-MI patients as well, those without HF symptoms or cardiac dysfunction. Larger trials, however, explicitly powered to assess these questions are needed to fully understand the safety and efficacy of SGLT2 inhibitors after MI," the editorialists wrote.

To that end, the ongoing large and trials are both enrolling MI survivors with new cardiac dysfunction to test SGLT2 inhibition in this setting.