SGLT2i therapy improves NT-proBNP after AMI

Empagliflozin in acute myocardial infarction: the EMMY trial

Literature - Von Lewinski D, Kolesnik E, Tripolt NJ, et al. - Eur Heart J. 2022 Aug 29;ehac494 [Online ahead of print]. doi: 10.1093/eurheartj/ehac494

Introduction and methods


SGLT2is have been shown to reduce the risk of HF hospitalization and death in patients with symptomatic HF [1-4,5]. As 15% of MI patients develop symptomatic HF and/or reduced EF within 1 year [6,7], it is pivotal to determine whether initiating SGLT2i treatment early after an MI is effective and safe.

Aim of the study

The authors aimed to investigate the effect of empagliflozin treatment initiated within 72 hours after PCI on cardiac function and HF biomarkers in patients with a recent large acute MI (AMI).


The EMMY (Empagliflozin in Patients With Acute Myocardial Infarction) study was a prospective, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial that was conducted in Austria. In this trial, 476 patients with a large AMI (creatine kinase >800 IU/L) and hs-troponin T/I level >10-fold the upper limit of normal were randomized to empagliflozin 10 mg once daily or placebo within 72 hours after PCI. In addition, patients received post-MI therapy as recommended by the 2017 ESC Guidelines [8]. Both patients with and without T2DM were included.


The primary efficacy endpoint was the change in NT-proBNP levels from randomization to week 26. Secondary efficacy endpoints included changes in functional and structural echocardiographic parameters, consisting of E/e’ ratio (to assess LV diastolic function), LV end-systolic volume (LVESV), and LV end-diastolic volume (LVEDV); changes in ketone body and glycated hemoglobin concentrations; and changes in body weight. Additional exploratory endpoints were hospitalization due to HF or other causes, duration of hospital stay, and all-cause mortality.

Key safety endpoints were the incidences of serious adverse events (SAEs), severe hypoglycemic events, genital infections, ketoacidotic events, and acute liver or renal injury.

Main results

Primary efficacy endpoint

  • Throughout the study, mean NT-proBNP levels decreased in both the empagliflozin and placebo group, but the decrease was larger in the empagliflozin group.
  • After adjusting for baseline NT-proBNP concentration, sex, and DM status, the reduction in NT-proBNP level at 26 weeks was greater in the empagliflozin group compared with the placebo group (mean difference: –15%; 95%CI: −23.6 to −4.4; P=0.026).

Secondary efficacy endpoints

  • LV systolic and diastolic functions improved in the empagliflozin and placebo groups over the course of the trial.
  • Compared with the placebo group, absolute LVEF improvement was 1.5% greater (95%CI: 0.2–2.9; P=0.029) in the empagliflozin group at 26 weeks.
  • Mean reduction in E/e′ ratio was 6.8% larger (95%CI: 1.3–11.3; P=0.015) in the empagliflozin-treated patients at 26 weeks compared with the placebo-treated patients.
  • At 26 weeks, reductions in LVESV (mean difference: –7.5 mL; 95%CI: –11.5 to –3.4; P=0.0003) and LVEDV (mean difference: –9.7 mL; 95%CI: –15.7 to –3.7; P=0.0015) were greater in the empagliflozin group compared with the placebo group.
  • The level of beta-hydroxybutyrate—the most common ketone body—showed a greater increase in the empagliflozin group compared with placebo at 26 weeks (difference : 41.9%; 95%CI: 21.8–63.8; P<0.0001).
  • In the small subgroup of T2DM patients, there was no significant between-group difference in the degree of HbA1c lowering at 26 weeks (P=0.11).
  • Body weight decreased more in the empagliflozin group (difference : −1.76 kg; 95%CI: −3.27 to −0.25; P=0.022).
  • Median duration of hospital stay due to AMI was 6.0 days (IQR: 3–9) in the empagliflozin group as well as the placebo group (P=0.40).

Safety endpoints

  • There were 72 SAEs in total; the number of SAEs did not differ between the empagliflozin and placebo groups.
  • HF hospitalization occurred in 7 patients (3 in empagliflozin group and 4 in placebo group).
  • During the study, 3 patients died (all in empagliflozin group). All deaths were considered to be unrelated to the study medication.
  • Other predefined safety outcomes were rare, and their number did not differ significantly between the two groups.
  • During the follow-up, no amputations, ketoacidosis, or severe hypoglycemic episodes were reported.


In patients with an AMI, empagliflozin treatment initiated within 72 hours after PCI was associated with a greater NT-proBNP reduction over 26 weeks compared with placebo. This decline was accompanied by an improvement in functional and structural echocardiographic parameters. In addition, there were no evident safety risks with empagliflozin.


1. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413–1424.

2. McMurray JJV, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381:1995–2008.

3. Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020;396:819–829.

4. Gager GM, Gelbenegger G, Jilma B, von Lewinski D, Sourij H, Eyileten C, et al. Cardiovascular outcome in patients treated with SGLT2 inhibitors for heart failure: a meta-analysis. Front Cardiovasc Med. 2021;8:691907.

5. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Bohm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385:1451–1461.

6. Carvalho LSF, Bogniotti LAC, de Almeida OLR, E Silva JCQ, Nadruz W, Coelho OR, et al. Change of BNP between admission and discharge after ST-elevation myocardial infarction (Killip I) improves risk prediction of heart failure, death, and recurrent myocardial infarction compared to single isolated measurement in addition to the GRACE score. Eur Heart J Acute Cardiovasc Care. 2019;8:643–651.

7. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation. 2019;139:e56–e528.

8. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2017;39:119–177.

Find this article online at Eur Heart J.

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