Early Signal of Benefit for Empagliflozin in Acute MI: EMMY

Early use of the SGLT2 inhibitor empagliflozin (Jardiance) after an acute myocardial infarction (MI) improves natriuretic peptide levels and markers of cardiac function and structure, new randomized trial results show.

SGLT2 inhibitors have shown benefits in patients with heart failure (HF) across the spectrum of left ventricular function, reducing the risk for HF hospitalization and cardiovascular death in low ejection fraction (EF) in last year’s EMPEROR-Preserved and the newly reported DELIVER trial. SGLT2 inhibitors also lower the risk for incident HF in such high-risk groups as those with type 2 diabetes or chronic kidney disease.

Keeping in mind that benefits emerge within weeks, regardless of the trial, and that MI is a major cause for incident heart failure, “it was, of course, intriguing to ask whether an SLGT2 inhibitor treatment would have beneficial effects if started right after an acute myocardial infarction. But those data are lacking,” explained study author Harald Sourij, MD, MBA, Medical University of Graz, Austria.

Enter the double-blind EMMY trial, which was conducted at 11 Austrian sites from May 2017 to May 2022 and randomly assigned 476 patients within 72 hours of percutaneous coronary intervention for an acute MI to receive empagliflozin 10 mg once daily or matching placebo. This was on top of guideline-directed post-MI therapy, which included antiplatelet drugs (100%), statins (97%), and angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers (96%).

Their median age was 57 years, 13% had type 2 diabetes, 11% had a history of coronary artery disease, and 4.8% a history of MI. Median N-terminal pro b-type natriuretic peptide (NT-pro-BNP) was 1294 pg/mL.

NT-pro-BNP levels declined from baseline in both groups, but the primary outcome of mean change at week 26 was 15% lower in the empagliflozin group, after adjustment for baseline NT-proBNP concentration, sex, and diabetes status (P = .026).

The reduction with empagliflozin was already a significant 13% lower at 12 weeks and was confirmed in sensitivity analyses, Sourij said during a late-breaking session at the European Society of Cardiology 2022 Congress. The findings were also published simultaneously in the European Heart Journal.

Left ventricular EF improved in both groups, with those assigned to empagliflozin having a 1.5% absolute higher EF at week 26 (P = .029). The E/e′ ratio was significantly improved, being 6.8% lower than placebo (P = .015).

The structural markers of left ventricular end systolic volume (–7.5 mL; P = .0003) and LV end diastolic volume (–9.7 mL; P = .0015) improved as well, and were smaller in the empagliflozin group.

There were three deaths during the study, all in the empagliflozin arm. All three were considered unrelated to treatment by the adjudication committee prior to unblinding, Sourij said.

Hospitalizations for HF were very low in both groups, with three in the empagliflozin arm and three in the placebo arm, with no amputations, ketoacidosis, or severe glycemic episodes. Urinary tract infections (11 vs 7) and fungal infections (7 vs 2) were more common with the SGLT2 inhibitor.

Not Without Limitations

Although not without limitations, the study “represents an important step forward for SGLT2 inhibitors in the post-MI population,” Josephine Harrington, MD, Duke University, Durham, North Carolina, and colleagues write in an accompanying editorial.

They point out that the study assessed the benefit of empagliflozin on surrogate markers of HF after MI and had a relatively homogenous patient population, further limited by the fact that only 18% of participants were women.

The population was also relatively low risk, with a median baseline EF of almost 50% and estimated glomerular filtration rate (eGFR) of more than 45 mL/min per 1.73 m² (median, 90 mg/min per 1.73 m²).

Although the overall impact on natriuretic peptide was modest, previous SGLT2 trials in HF have reported similar proportional decreases that were associated with improved clinical outcomes, Harrington notes. Changes in EF and ventricular volumes comparable to those in EMMY have also been associated with cardiovascular and mortality benefits.

These findings “increase our optimism that these drugs may provide clinical benefit to the post-MI population,” the editorialists write.

Further insights will be provided by the ongoing DAPA-MI and EMPACT-MI trials, which will test whether dapagliflozin and empagliflozin, respectively, can lower the risk for HF hospitalization and death in patients with new cardiac dysfunction after MI. EMPACT-MI will additionally evaluate patients with preserved EF but new and acute signs of HF in the setting of MI.

Both trials are enrolling patients with an eGFR down to 20 mL/min per 1.73 m², “enabling a broad evaluation of the possible renal safety and efficacy of SGLT2 inhibitors,” Harrington and colleagues write. The trials are expected to be completed in 2023.

The study was funded by Boehringer Ingelheim, and NT-pro-BNP Elecsys kits were provided by Roche Diagnostics Austria. Sourij is on the advisory board and speakers bureau of Boehringer Ingelheim, NovoNordisk, Sanofi-Aventis, Amgen, AstraZeneca, Bayer, Eli Lilly, Kapsch, MSD, and Daiichi Sankyo. Coauthor disclosures are listed in the publication. Harrington receives salary support from a T32 training grant.

Eur Heart J. Published August 29, 2022. Full text, Editorial

European Society of Cardiology (ESC) Congress 2022. Presented August 29, 2022.

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