Effect of Dapagliflozin on Myocardial Fibrosis After STEMI: A Double-Blind, Placebo-Controlled Randomized Trial

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.