Clinical question: Does starting empagliflozin for patients with acute myocardial infarction (AMI) and new onset systolic heart failure (HF) or congestive symptoms reduce the risk of first hospitalization for heart failure or death from any cause?
Background: After AMI, patients are at increased risk for HF and death, especially if they present with congestive symptoms or a decreased left ventricular ejection fraction (LVEF). Empagliflozin improves cardiovascular outcomes for patients with type 2 diabetes, chronic kidney disease, and HF. The empagliflozin in acute myocardial infarction (EMMY) trial showed that in patients with a recent MI, empagliflozin was associated with a reduction in natriuretic peptide and improvement in echocardiographic parameters. The EMPACT-MI trial assessed whether empagliflozin lowers the risk of first hospitalization for HF and all-cause mortality in patients with AMI.
Study design: International, event-driven, double-blind, randomized, and placebo-controlled
Setting: 451 sites in 22 countries in North America, Latin America, Europe, and Asia from December 2020 to March 2023
Synopsis: EMPACT-MI enrolled patients with AMI, either ST-elevation myocardial infarction (75%) or non-ST elevation myocardial infarction (25%), with new onset LVEF <45% or treatment for congestion. Patients with prior chronic HF or already on sodium-glucose transport protein 2 inhibitor therapy were excluded. Participants had to have more than one additional risk factor for HF hospitalization or death, such as age ≥65, LVEF <35%, 3-vessel coronary artery disease, prior MI, atrial fibrillation, or type 2 diabetes.
Within 14 days of the AMI, patients were randomized to empagliflozin versus placebo (3,260 versus 3,262). During a median follow-up of 17.9 months, the incidence of first hospitalization for HF or all-cause mortality (primary outcome) was 5.9 versus 6.6 events per 100 patient-years for empagliflozin and placebo groups, respectively (HR, 0.9; 95% CI, 0.76 to 1.06; P=0.21). Of the components of the primary outcome, first hospitalization for HF was decreased in the empagliflozin group (3.6% versus 4.7%; HR, 0.77; 0.95% CI, 0.6 to 0.98). There was no difference in all-cause mortality (5.2% versus 5.5%; HR, 0.96; 95%CI, 0.78 to 1.19). Limitations included the timing of the study during the COVID-19 pandemic when HF hospitalizations were substantially lower.
Bottom line: Early initiation of empagliflozin after AMI with new-onset systolic HF or signs and symptoms of congestion did not reduce a composite outcome of first hospitalization for HF or death from any cause.
Citation: Butler J, et al. Empagliflozin after acute myocardial infarction. N Engl J Med. 2024;390(16):1455-66.
Dr. Sokolova
Dr. Sokolova is a hospitalist in the division of hospital medicine at the Mount Sinai Health System and an assistant professor of medicine at the Icahn School of Medicine at Mount Sinai in New York.