Weekly Journal Scan: sodium/glucose cotransporter 2 inhibition after myocardial infarction still in the grey area

Key points• The EMPACT-MI trial (Study to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) was a company-funded, multi-centre, double-blind, randomized, placebo-controlled trial to test the hypothesis that sodium/glucose cotransporter 2 (SGLT2) inhibition with empagliflozin would reduce the risk of hospitalization for heart failure (HF) or death among patients with acute myocardial infarction (AMI) and either a new reduction in left ventricular ejection fraction (LVEF) or signs or symptoms of congestion (or both). 1 • A total of 6522 patients (mean age, 64 years) were recruited from December 2020 through March 2023, at 451 sites in 22 countries, who had been hospitalized with AMI within 14 days before randomization and had either evidence of a newly developed LVEF < 45% or signs or symptoms of congestion that triggered in-hospital treatment (or both).Patients who met these eligibility criteria were randomized in a 1:1 ratio to receive empagliflozin 10 mg daily or placebo, in addition to standard care.• EMPACT-MI adopted an event-driven design, whereby 532 patients with a primary endpoint event of hospitalization for HF or death from any cause would provide the trial with 85% power to detect a 23% lower risk of an event in the empagliflozin group than in the placebo group, with a two-sided type 1 error of 0.05.• The median time from admission to randomization was 5 days.Three out of four patients had an LVEF of <45%, and over half had signs or symptoms of congestion that triggered treatment during the index hospitalization.The prevalent clinical presentation was ST-segment elevation MI, and revascularization for the index MI was performed in almost 90%.• Over an 18-month follow-up, a primary endpoint event occurred in 267 of 3260 patients (8.2%) in the empagliflozin group and in 298 of 3262 patients (9.1%) in the placebo group, with incidence rates of 5.9 and 6.6 events, respectively, per 100 patient-years [hazard ratio (HR), 0.90; 95% confidence interval (CI), 0.76-1.06;P = .21].Results were consistent across a number of pre-specified subgroups, including age, baseline estimated glomerular filtration rate, type 2 diabetes, blood pressure, LVEF, and use of various concomitant treatments.A first hospitalization for HF was recorded in 118 patients (3.6%) in the empagliflozin group and in 153 patients (4.7%) in the placebo group (HR, 0.77; 95% CI, 0.60-0.98),and death from any cause occurred in 169 (5.2%) and 178 (5.5%), respectively (HR, 0.96; 95% CI, 0.78-1.19).The rates of pre-specified key secondary endpoint events did not differ substantially in the two trial groups.Serious adverse events were consistent with the known safety profile of empagliflozin and were recorded in about one-quarter of patients in both groups.