Published in Congress: ACC 2024

Study Design: The study was presented at ACC.24 and simultaneously published in the New England Journal of Medicine.

Empagliflozin has demonstrated efficacy in enhancing cardiovascular outcomes for patients with heart failure (HF), individuals with type 2 diabetes mellitus (T2DM) at heightened cardiovascular risk, and those afflicted with chronic kidney disease. However, the safety and effectiveness of empagliflozin in patients who have undergone an acute myocardial infarction (AMI) remain inadequately understood. Hence, the EMPACT-MI trial endeavors to fill this knowledge void by investigating its potential in this specific patient population.

The objective of the study is to determine whether empagliflozin reduces the risk of first hospitalization for HF or death in patients at risk of HF following an AMI and to assess the potential benefits and risks of empagliflozin in this population.

Conducted as a double-blind, event-driven trial, the study was carried out across 451 centers in 22 countries from December 2020 to March 2023. A total of 6,522 patients hospitalized due to AMI were treated with either daily 10 mg empagliflozin or placebo in addition to standard care within 14 days of admission. Primary outcomes included first hospitalization for HF or death from any cause, while secondary outcomes encompassed all-cause mortality rate, first hospitalization for HF, and total hospitalizations for HF.

The mean follow-up duration was 17.9 months. Initially, 78.4% of patients had left ventricular ejection fraction (LVEF) ?45%, and 57.0% exhibited signs or symptoms of congestion requiring treatment during index hospitalization. There was no statistically significant difference observed between empagliflozin and placebo in terms of primary outcomes (HR: 0.90, 95% CI 0.76-1.06, p=0.21). Upon examination of secondary outcomes, while the all-cause mortality rate was lower in the empagliflozin group compared to placebo, this difference was not statistically significant (5.2% vs. 5.5%, HR: 0.96, 95% CI 0.78-1.19, p=0.73). However, rates of first hospitalization for HF (23%) and total hospitalizations for HF (33%) were significantly lower in the empagliflozin group compared to placebo, and these differences were statistically significant (HR: 0.77, 95% CI 0.60-0.98, p = 0.031 and HR: 0.67, 95% CI 0.51-0.89, p=0.006, respectively). The effect of treatment on first and total hospitalizations for HF was consistent across LVEF, congestion status, and their combination. In terms of safety outcomes, empagliflozin led to fewer adverse events requiring drug discontinuation compared to placebo.

The study demonstrates that early administration of empagliflozin following AMI is ineffective in reducing all-cause mortality and first hospitalization for HF. However, secondary analyses suggest that empagliflozin may reduce hospitalizations for HF, particularly in AMI patients with increased risk of HF.

These findings suggest that while supporting routine use of Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, initiating this treatment shortly after recent myocardial infarction, especially in patients with indications such as T2DM or chronic kidney disease, may prove beneficial. This approach is believed to potentially mitigate the risk of HF. It indicates that empagliflozin could be considered as a potential treatment option for AMI patients at high risk of HF. Nonetheless, further research and clinical trials are warranted.