N Engl J Med 2024;390:1455-1466BackgroundDespite advances in the care of patients after myocardial infarction, there remains residual risk of heart failure and death. The amount of risk parallels the degree of left ventricular systolic dysfunction. Previous studies have shown that the drug class of sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular risk (especially recurrent heart failure) in multiple clinical situations.The goal of the placebo-controlled Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction (EMPACT-MI) trial was to determine whether empagliflozin reduced the risk of heart failure or death in patients with acute MI and either a new reduction in LV function or signs of congestion, or both.PatientsAdult patients who had been hospitalized with MI within 14 days before randomization. There had to be a new LVEF <45% or signs/symptoms of congestion that resulted in treatment during the index hospital admission.There also had to be another risk factor, which the authors wrote that enriched the risk for heart failure or death. This could include many things: age of 65 years or older; a newly developed LVEF < 35%; a history of MI, atrial fibrillation, or type 2 diabetes; an estimated glomerular filtration rate (GFR) of less than 60 ml per minute per 1.73 m2 of body-surface area; an elevated natriuretic peptide or uric acid level; an elevated pulmonary artery or right ventricular systolic pressure; three-vessel coronary artery disease; peripheral artery disease; or no revascularization for the index myocardial infarction.The key exclusion criteria was the a previous diagnosis of heart failure or any reason that the patient was planning to take SGLT2i.Baseline CharacteristicsThe average age of patients was 63 years. Only a quarter were women. More than 80% were white. Approximately 75% of patients had STEMI, the rest, NSTEMI. A total of 78% of the patients had a LVEF < 45%, and 57% had signs or symptoms of congestion that resulted in treatment during the index hospitalization. For the patients with signs or symptoms of congestion, only 20% had a LVEF of at least 45%. The most common enrichment factors were age > 65 (50%), Type 2 DM (32%) and 3-vessel CAD (31%). Slightly more than 70% of patients had more than one enrichment factor.Approximately 20% of patients had an LVEF > 45%. Slightly more than half of patients had an LVEF between 35% and 45%. Trial ProceduresRandomization was 1:1 to empagliflozin 10mg daily or matching placebo. The trial was conducted between 2020-2023 at 451 sites in 22 countries. The median time from admission to randomization was 5 days. The trial had a streamlined design, with the collection of essential data only, including information about specific safety events, and mainly remote follow-up of patients (by means of a Web-based application or a telephone call) with only a few face-to-face visits; the trial assessed investigator-reported end-point events rather than centrally adjudicated end-point events. Specifically, follow up included a remote visit at 2 weeks, a face-to-face visit at 6 months, and remote visits every 6 months thereafter until the end of the trial, when a final telephone call was performed.EndpointsThe primary end point was a composite of hospitalization for heart failure or death from any cause as assessed in a time-to-first-event analysis.The key secondary end points in the prespecified hierarchical testing strategy were the total number of hospitalizations for heart failure or death from any cause, the total number of nonelective cardiovascular hospitalizations or death from any cause, the total number of nonelective hospitalizations for any cause or death from any cause, and the total number of hospitalizations for myocardial infarction or death from any cause. Trial authors estimated that 532 patients with a primary end-point event would provide the trial with 85% power to detect a 23% lower ris