Background: Myocardial fibrosis leads to ventricular dysfunction and worsened prognosis, especially after ST-segment elevation myocardial infarction (STEMI). Sodium–glucose cotransporter 2 inhibitors (SGLT2is) offer cardiovascular benefits by reducing markers of myocardial fibrosis and fibroblast activity. However, the effects of SGLT2i on myocardial fibrosis deposition among STEMI patients undergoing primary percutaneous coronary intervention (PCI) have not yet been evaluated. Study and Design: The effect of DAPAgliflozin on myocardial fibrosis and ventricular function in patients with STEMI (DAPA-STEMI) trial is a phase III, multicenter, randomized, double-blind, placebo-controlled trial. The study aims to assess the effects of dapagliflozin on myocardial fibrosis and ventricular function, evaluated using cardiac magnetic resonance (CMR), in STEMI patients undergoing primary PCI. Eligible patients were 30 to 85 years old and exhibited a left ventricular ejection fraction ≤ 50%. A total of 120 patients with STEMI were expected to be randomized 1:1 to receive dapagliflozin 10 mg or placebo daily for six months. The primary endpoint is the change in the extracellular volume fraction of the remote myocardium from baseline to six months, as measured by CMR. The secondary endpoints include changes in the circulating C-terminal propeptide of type I procollagen, N-terminal propeptide of type III procollagen, and Galectin-3 from baseline to six months. The study was stopped prematurely due to slow recruitment, with 54 enrolled patients, limiting the statistical power to detect changes in the primary endpoint between groups. Conclusions: The DAPA-STEMI trial will provide insights into the impact of dapagliflozin on myocardial fibrosis and ventricular remodeling in patients with STEMI undergoing primary PCI. Clinical Trial Registration Unique Identifier: NCT06619600

Background: Myocardial fibrosis plays a key role in adverse remodeling after ST-segment-elevated myocardial infarction (STEMI). The effect of sodium–glucose cotransporter 2 inhibitors (SGLT2is) on myocardial fibrosis deposition among patients with STEMI undergoing primary percutaneous coronary intervention (pPCI) is unclear. Objectives: To assess the effects of SGLT2is on myocardial fibrosis among patients with STEMI undergoing pPCI. Methods: Patients with STEMI undergoing pPCI with left ventricular ejection fraction ≤ 50% were randomized to dapagliflozin 10 mg or placebo. The primary endpoint was cardiac magnetic resonance (CMR)-derived 6-month changes in remote myocardium extracellular volume (ECV) fraction from baseline. Secondary endpoints included changes in CMR-derived myocardial volumes, change in serum fibrosis biomarker levels, and adverse events. Multivariable adjustment for infarction location and diabetes status was performed as sensitivity. The study was halted prematurely due to slow recruitment. Results: Fifty-two patients underwent randomization between May 2021 and April 2024 and completed follow-up. At 6 months, dapagliflozin resulted in a non-significant reduction in ECV change compared to placebo (−0.39 [4.7] vs. 1.43 [5.7]; difference: −1.82 [−4.86; 1.23]; p-value = 0.235) while also leding to a higher degree of reduction in N-terminal pro-peptide of type III collagen (−177.0 pg/mL [416.1] vs. 3.6 pg/mL [553.8]; p-value = 0.208). No significant differences in other biomarkers or adverse events were noted in the main analysis. After adjustment, dapagliflozin was associated with increased reduction in left ventricular end-systolic volume (−4.02 mL [7.4] vs. 0.10 mL [10.1]; difference: −4.92 [−9.8; −0.1]; p-value = 0.047). Conclusions: In STEMI patients undergoing pPCI, dapagliflozin did not result in a significant reduction in ECV or biomarkers of fibrosis at 6 months.